Melanoma cells can be eliminated by sialylated CD43 × CD3 bispecific T cell engager formats in vitro and in vivo.

Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation. Here we observed that AT1413 binds also to certain non-hematopoietic tumor cells, particularly melanoma and breast cancer. AT1413 immune precipitated CD43s from melanoma cells confirming that it recognizes the same target on melanoma as on AML. AT1413 induced antibody-dependent cellular cytotoxicity against short-term cultured patient-derived melanoma samples. However, AT1413 was unable to affect the growth of melanoma cells in vivo. To increase the efficacy of AT1413 as a therapeutic antibody, we generated two different formats of bispecific T-cell engaging antibodies (TCEs): one binding bivalently (bTCE) and the other monovalently (knob-in-hole; KiH) to both CD43s and CD3ε. In vitro, these TCEs redirected T-cell cytotoxicity against melanoma cells with differences in potencies. To investigate their effects in vivo, we grafted mice that harbor a human immune system with the melanoma cell line A375. Treatment with both AT1413 bTCE and AT1413 KiH significantly reduced tumor outgrowth in these mice. These data indicate a broad therapeutic potential of AT1413 that includes AML and CD43s-expressing solid tumors that originate from CD43-negative tissues.

Helicobacter pylori infection is not associated with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is an autoinflammatory disease caused by genetic susceptibility and environmental triggers, which include infectious agents. Helicobacter pylori, a bacterium that frequently colonizes the stomach, is associated with the development of certain autoinflammatory disorders. This study examined a possible association between H. pylori infection and RA. METHOD: This cohort study was performed in the Central Denmark Region. Patients were enrolled from primary healthcare centres after a urea breath test (UBT) for H. pylori and followed for a median of 8 years. Nationwide administrative registries provided information about the patients' diagnoses, country of birth, and gender. Comorbidity was determined using the Charlson Comorbidity Index. We compared the prevalence of RA via odds ratios (ORs) and incidences using Cox regression to calculate the hazard ratios (HRs) by comparing H. pylori-positive and H. pylori-negative individuals and adjusting for confounding variables. RESULTS: A total of 56 000 people diagnosed as H. pylori positive or negative had similar rates of comorbidity. No link was found between H. pylori and RA. There was no difference in RA prevalence until time of UBT [OR = 0.91, 95% confidence interval (CI) 0.70-1.19)] or incidence of new RA cases after UBT (HR = 0.80, 95% CI 0.56-1.13) between H. pylori-positive and -negative subjects. Validation via four other RA definitions provided similar results. CONCLUSION: This study found no association between H. pylori infection and RA. This result does not support the involvement of H. pylori in a gut-joint axis of importance for RA development.

Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP-1). The protocol was evaluated in anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3- (n = 9) and placebo-treated (n = 9) CD patients. Anti-VDR-stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4(+) T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4(+) T cells increased following stimulation. This VDR up-regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0027). VDR expression was correlated with in-vitro interferon-γ production in stimulated PBMCs (P = 0.01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor-mediated VDR up-regulation.

Magnetic Resonance Imaging with a Weak Albumin Binding Contrast Agent can Reveal Additional Endoleaks in Patients with an Enlarging Aneurysm after EVAR.

OBJECTIVES/BACKGROUND: To examine the additional diagnostic value of magnetic resonance imaging (MRI) after administration of a weak albumin binding contrast agent in post-endovascular aneurysm repair (EVAR) patients with aneurysm growth with no or uncertain endoleak after computed tomography angiography (CTA). METHODS: This was a prospective diagnostic cross sectional study carried out between April 2011 and August 2013. MRI was performed in all patients with aneurysm growth≥5 mm after EVAR implantation and no or uncertain endoleak on CTA, or the inability, on CTA, to identify the source of a visible endoleak. All MRI scans were performed on a 1.5 T clinical MRI scanner after administration of a weak albumin binding contrast agent. The presence of endoleaks was assessed by visually comparing pre- and post-contrast T1-weighted images with fat suppression. Post-contrast images were acquired 5 and 15 minutes after contrast administration. RESULTS: Twenty-nine patients (26 men; 90%) with a median age of 74 years (interquartile range [IQR] 67-76) were included. The median interval between EVAR and MRI was 39 months (IQR 20-50). The median increase in maximum aneurysm diameter during total follow up after EVAR was 11 mm (IQR 6-17). At CTA, 16 patients (55%) had no detectable endoleak, five patients (17%) had suspected but uncertain endoleak, and eight patients had a definite endoleak (28%). On the post-contrast MRI images, endoleak was observed in 24 patients (83%). In all patients with uncertain endoleak on CTA, endoleak was detected with MRI. For type II endoleaks, feeding vessels were detected in 22/23 patients (96%) and these were all, except one, lumbar arteries. CONCLUSION: In patients with enlarging aneurysms of unknown origin after EVAR, MRI with a weak albumin binding contrast agent has additional value for both the detection and determination of the origin of the endoleak.

Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) can be effectively applied for longitudinal cohort evaluation of articular cartilage regeneration.

OBJECTIVE: Delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) facilitates non-invasive evaluation of the glycosaminoglycan content in articular cartilage. The primary aim of this study was to show that the dGEMRIC technique is able to monitor cartilage repair following regenerative cartilage treatment. DESIGN: Thirty-one patients with a focal cartilage lesion underwent a dGEMRIC scan prior to cartilage repair surgery and at 3 and 12 months follow-up. At similar time points clinical improvement was monitored using the Knee injury and Osteoarthritis Outcome Score (KOOS) and Lysholm questionnaires. Per MRI scan several regions-of-interest (ROIs) were defined for different locations in the joint. The dGEMRIC index (T1gd) was calculated for each ROI. Repeated-measures analysis of variance (RMANOVA) analysis was used to evaluate improvement in clinical scores and MRI T1gd over time. Also regression analysis was performed to show the influence of local repair on cartilage quality at distant locations in the knee. RESULTS: Clinical scores and the dGEMRIC T1gd per ROI showed a statistically significant improvement (P < 0.01), from baseline, at 12 months follow-up. Also, improvement from baseline in T1gd of the ROI defining the treated cartilage defect showed a direct relationship (P < 0.007) to the improvement of the T1gd of ROI at other locations in the joint. CONCLUSIONS: The dGEMRIC MRI protocol is a useful method to evaluate cartilage repair. In addition, local cartilage repair influenced the cartilage quality at other location in the joint. These findings validate the use of dGEMRIC for non-invasive evaluation of the effects of cartilage regeneration.

Magnetic resonance imaging is more sensitive than computed tomography angiography for the detection of endoleaks after endovascular abdominal aortic aneurysm repair: a systematic review.

OBJECTIVES: The purpose of this systematic review was to examine whether magnetic resonance imaging (MRI) or computed tomography angiography (CTA) is more sensitive for the detection of endoleaks in patients with abdominal aortic aneurysm (AAA) after EVAR. DESIGN: Systematic review. MATERIALS AND METHODS: A systematic electronic search was performed. Articles were included when post-EVAR patients were evaluated by both MRI as index test and CTA as comparison. Methodological quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Primary outcome was the proportion of patients in whom MRI detected additional endoleaks, which were not seen with CTA. RESULTS: Eleven articles were included. The overall methodological quality of the articles was good. In total, 369 patients with 562 MRI and 562 CTA examinations were included. A total of 146 endoleaks were detected by CTA; MRI detected all but two of these endoleaks. With MRI 132 additional endoleaks were found. CONCLUSIONS: MRI is more sensitive compared to CTA for the detection of post-EVAR endoleaks, especially for the detection of type II endoleaks. MRI should be considered in patients with continued AAA growth and negative or uncertain findings at CTA.

Evaluation Metrics for Augmented Reality in Neurosurgical Preoperative Planning, Surgical Navigation, and Surgical Treatment Guidance: A Systematic Review.

BACKGROUND AND OBJECTIVE: Recent years have shown an advancement in the development of augmented reality (AR) technologies for preoperative visualization, surgical navigation, and intraoperative guidance for neurosurgery. However, proving added value for AR in clinical practice is challenging, partly because of a lack of standardized evaluation metrics. We performed a systematic review to provide an overview of the reported evaluation metrics for AR technologies in neurosurgical practice and to establish a foundation for assessment and comparison of such technologies. METHODS: PubMed, Embase, and Cochrane were searched systematically for publications on assessment of AR for cranial neurosurgery on September 22, 2022. The findings were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: The systematic search yielded 830 publications; 114 were screened full text, and 80 were included for analysis. Among the included studies, 5% dealt with preoperative visualization using AR, with user perception as the most frequently reported metric. The majority (75%) researched AR technology for surgical navigation, with registration accuracy, clinical outcome, and time measurements as the most frequently reported metrics. In addition, 20% studied the use of AR for intraoperative guidance, with registration accuracy, task outcome, and user perception as the most frequently reported metrics. CONCLUSION: For quality benchmarking of AR technologies in neurosurgery, evaluation metrics should be specific to the risk profile and clinical objectives of the technology. A key focus should be on using validated questionnaires to assess user perception; ensuring clear and unambiguous reporting of registration accuracy, precision, robustness, and system stability; and accurately measuring task performance in clinical studies. We provided an overview suggesting which evaluation metrics to use per AR application and innovation phase, aiming to improve the assessment of added value of AR for neurosurgical practice and to facilitate the integration in the clinical workflow.

dGEMRIC as a tool for measuring changes in cartilage quality following high tibial osteotomy: a feasibility study.

OBJECTIVE: The high tibial osteotomy (HTO) is an effective strategy for treatment of painful medial compartment knee osteoarthritis. Effects on cartilage quality are largely unknown. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables non-invasive assessment of cartilage glycosaminoglycan content. This study aimed to evaluate if dGEMRIC could detect relevant changes in cartilage glycosaminoglycan content following HTO. DESIGN: Ten patients with medial compartment osteoarthritis underwent a dGEMRIC scan prior to HTO, and after bone healing and subsequent hardware removal. A dGEMRIC index (T1Gd) was used for changes in cartilage glycosaminoglycan content, a high T1Gd indicating a high glycosaminoglycan content and vice versa. Radiographic analysis included mechanical axis and tibial slope measurement. clinical scores [knee osteoarthritis outcome scale (KOOS), visual analogue score (VAS) for pain, Knee Society clinical rating system (KSCRS)] before, 3 and 6 months after HTO and after hardware removal were correlated to T1Gd changes. RESULTS: Overall a trend towards a decreased T1Gd, despite HTO, was observed. Before and after HTO, lateral femoral condyle T1Gd was higher than medial femoral condyle (MFC) T1Gd and tibial cartilage T1Gd was higher than that of femoral cartilage (P < 0.001). The MFC had the lowest T1Gd before and after HTO. Clinical scores all improved significantly (P < 0.01), KOOS Symptoms and QOL were moderately related to changes in MFC T1Gd. CONCLUSIONS: dGEMRIC effectively detected differences in cartilage quality within knee compartments before and after HTO, but no changes due to HTO were detected. Hardware removal post-HTO seems essential for adequate T(1)Gd interpretation. T(1)Gd was correlated to improved clinical scores on a subscore level only. Longer follow-up after HTO may reveal lasting changes. ClinicalTrials.gov registration ID: NCT01269944.

Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy.

OBJECTIVE: The purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids. METHODS: Thirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay. RESULTS: The mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days. CONCLUSION: This prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids. KEY POINTS: • Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids. • Volumetric feedback ablation is a novel technology that allows larger treatment volumes • MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback.

Feasibility of bone density evaluation using plain digital radiography.

OBJECTIVE: For the radiographic evaluation of subchondral bone changes (sclerosis) in osteoarthritis (OA), bone density (BD) is commonly subjectively assessed. BD evaluation using plain digital radiography might be influenced by acquisition and post-processing (PP) settings. Objective of this study was to evaluate the effects of these settings on the measurement of BD using digital radiographs. METHODS: A bone density standard (BDS) of hydroxyapatite (HA) mimicked a BD range of 1.0-5.75 g/cm(2). Digital radiographs were acquired with variation in acquisition settings, and with clinical and minimal PP. An aluminum step wedge served as an internal reference to express the gray values of the BDS in mm aluminum equivalents (mmAl). The relation (R(2)) between actual BD and BD normalized to the reference wedge was evaluated with linear regression analyses for radiographs with variations in PP and acquisition settings. Precision of BD measurement of the BDS was evaluated for application in clinical practice. RESULTS: The correlation between actual BD and BD normalized to the reference was improved by changing PP from clinical (R(2)=0.96) to minimal (R(2)=0.98). Higher tube voltage [kilovolt (kV)] improved the correlation further. Even for clinical PP, average standard deviation (SD) was 0.97 mmAl, much smaller than the change of 2.51 mmAl clinically observed in early OA, which implies the feasibility of BD measurements on digital radiographs. CONCLUSION: Changing PP and acquisition settings in clinical practice can have profound effect on outcome. If done with care, accurate BD measurement is feasible using plain digital radiography.

Pelvic rotation and tilt can cause misinterpretation of the acetabular index measured on radiographs.

BACKGROUND: Radiographic diagnosis and followup studies of developmental dysplasia of the hip are commonly performed by measuring the acetabular index on radiographs using Hilgenreiner's method. The outcome of the measurement, however, depends on the orientation of the subject's pelvis relative to the xray source. The influence of pelvic rotation and tilt on the measurement error has been evaluated separately but not in combination. QUESTIONS/PURPOSES: We asked whether (1) combinations of pelvic rotation and tilt introduced systematic error in acetabular index measurement in a reproducible way, and (2) ratios proposed to evaluate either pelvic rotation (R(rotation)) or pelvic tilt (R(tilt)) are influenced by pelvic tilt and rotation, respectively. METHODS: Radiographic measurements of the acetabular index, R(rotation), and R(tilt) were performed on digitally reconstructed radiographs of one high-resolution three-dimensional CT dataset with various combinations of pelvic rotation and tilt. RESULTS: For rotations and tilt up to 12°, the average systematic errors in the acetabular index varied from -8.8° to 4.5°. Negative and positive error values can be interpreted as underestimations and overestimations of the acetabular index, respectively. Errors in acetabular index measurements were acceptable for R(rotation) values between 1.0 and 2.0 and R(tilt) values between 1.1 and 1.8. CONCLUSIONS: To limit the systematic error in assessing the acetabular index caused by pelvic misalignment, we recommend only radiographs acquired with ± 4° rotation and ± 4° tilt be considered acceptable.

Robust initialization of 2D-3D image registration using the projection-slice theorem and phase correlation.

PURPOSE: The image registration literature comprises many methods for 2D-3D registration for which accuracy has been established in a variety of applications. However, clinical application is limited by a small capture range. Initial offsets outside the capture range of a registration method will not converge to a successful registration. Previously reported capture ranges, defined as the 95% success range, are in the order of 4-11 mm mean target registration error. In this article, a relatively computationally inexpensive and robust estimation method is proposed with the objective to enlarge the capture range. METHODS: The method uses the projection-slice theorem in combination with phase correlation in order to estimate the transform parameters, which provides an initialization of the subsequent registration procedure. RESULTS: The feasibility of the method was evaluated by experiments using digitally reconstructed radiographs generated from in vivo 3D-RX data. With these experiments it was shown that the projection-slice theorem provides successful estimates of the rotational transform parameters for perspective projections and in case of translational offsets. The method was further tested on ex vivo ovine x-ray data. In 95% of the cases, the method yielded successful estimates for initial mean target registration errors up to 19.5 mm. Finally, the method was evaluated as an initialization method for an intensity-based 2D-3D registration method. The uninitialized and initialized registration experiments had success rates of 28.8% and 68.6%, respectively. CONCLUSIONS: The authors have shown that the initialization method based on the projection-slice theorem and phase correlation yields adequate initializations for existing registration methods, thereby substantially enlarging the capture range of these methods.

The influence of different types of stent grafts on aneurysm neck dynamics after endovascular aneurysm repair.

OBJECTIVE: Dynamic imaging provides insight into aortic shape changes throughout the cardiac cycle. These changes may be important for proximal aortic stent graft fixation, sealing and durability. The objective of this study is to analyse the influence of different types of stent grafts on dynamic changes of the aneurysm neck. METHODS: Pre- and postoperative electrocardiography (ECG)-gated computed tomographic angiography (CTA) scans were obtained in 30 abdominal aortic aneurysm (AAA) patients, 10 each from three different types of stent grafts (10 Talent, Endurant, and Excluder). Each dynamic CTA dataset consisted of eight reconstructed images over the cardiac cycle. Aortic area and radius changes during the cardiac cycle were determined at two levels: (A) 3 cm above and (B) 1 cm below the lowermost renal artery. Radius changes were measured over 360 axes, and plotted in a polar plot. An ellipse was fitted over the plots to determine radius changes over the major and minor axis for assessment of the asymmetric aspect and most prominent direction of distension. RESULTS: Baseline characteristics did not differ significantly between the three groups. Preoperatively, the aortic area increased significantly (p < 0.001) over the cardiac cycle in all patients at both levels: (A) mean increase 8.3 +/- 4.1% (2.0-17.3%); (B) mean increase 5.9 +/- 4.2% (1.9-12.4%). The postoperative aortic area increase over the cardiac cycle did not differ significantly from preoperative increases: (A) mean increase 9.9 +/- 2.2% (4.4-20.0%); (B) mean increase 7.7 +/- 2.4% (3.8-12.4%). The difference between radius change over the major and minor axis was significant both pre- and postoperatively for all three stent grafts, indicating asymmetric distension. Suprarenal, the distension showed a tendency to right-anterior and infrarenal to left-anterior. The distension and direction of the aortic expansion was preserved after stent grafting. There were no differences between the three types of stent grafts regarding their impact on the aortic distension or direction of this distension. CONCLUSION: The aorta expands significantly and asymmetrically throughout the cardiac cycle. After implantation of abdominal aortic stent grafts, the aortic distension and direction of distension remain equally preserved in all three groups. The three stent graft types studied seem to be able to adapt to the asymmetric dynamic aortic shape changes.

Cartilage Quality (dGEMRIC Index) Following Knee Joint Distraction or High Tibial Osteotomy.

OBJECTIVE: High tibial osteotomy (HTO) and knee joint distraction (KJD) are treatments to unload the osteoarthritic (OA) joint with proven success in postponing a total knee arthroplasty (TKA). While both treatments demonstrate joint repair, there is limited information about the quality of the regenerated tissue. Therefore, the change in quality of the repaired cartilaginous tissue after KJD and HTO was studied using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). DESIGN: Forty patients (20 KJD and 20 HTO), treated for medial tibiofemoral OA, were included in this study. Radiographic outcomes, clinical characteristics, and cartilage quality were evaluated at baseline, and at 1- and 2-year follow-up. RESULTS: Two years after KJD treatment, clear clinical improvement was observed. Moreover, a statistically significant increased medial (Δ 0.99 mm), minimal (Δ 1.04 mm), and mean (Δ 0.68 mm) radiographic joint space width (JSW) was demonstrated. Likewise, medial (Δ 1.03 mm), minimal (Δ 0.72 mm), and mean (Δ 0.46 mm) JSW were statistically significantly increased on radiographs after HTO. There was on average no statistically significant change in dGEMRIC indices over two years and no difference between treatments. Yet there seemed to be a clinically relevant, positive relation between increase in cartilage quality and patients' experienced clinical benefit. CONCLUSIONS: Treatment of knee OA by either HTO or KJD leads to clinical benefit, and an increase in cartilage thickness on weightbearing radiographs for over 2 years posttreatment. This cartilaginous tissue was on average not different from baseline, as determined by dGEMRIC, whereas changes in quality at the individual level correlated with clinical benefit.

Aortic pulsatile distention in young healthy volunteers is asymmetric: analysis with ECG-gated MRI.

OBJECTIVE: Knowledge of aortic shape changes throughout the cardiac cycle can offer improved understanding of vascular pathophysiology and may have crucial impact on stentgraft design and EVAR durability. To understand underlying mechanisms of dynamic changes in aortic aneurysm (neck) morphology, the undiseased aorta has to be studied first. Objective is to visualize and characterize dynamic aortic shape changes in young healthy volunteers. MATERIALS AND METHODS: Fifteen healthy volunteers (7 male, median age 24 year, range 18-28) were scanned using ECG-gated balanced gradient-echo MRI, with 16 reconstructed cardiac phases. Transverse scans were made perpendicular to the aorta: (A) above the aortic bifurcation, (B) infrarenal, (C) juxtarenal, (D) suprarenal and (E) above the celiac trunk. After aortic lumen segmentation, radial changes during the cardiac cycle were measured, from the center of mass, over 360 degrees, and plotted. An ellipse was fitted over the distention plots, yielding the direction (AP:0 degrees, Right: -90 degrees, Left: 90 degrees ) and magnitude of radius change over the major and minor axis. RESULTS: Asymmetric distention was observed, with a variable rate per patient and level. Radius changes decreased from the proximal to distal aorta. Radius changes over the major axis ranged from 14% to 41%. At level A mean change in radius over the minor versus major axis was 1.4+/-0.2mm (17%) versus 1.6+/-0.2mm (20%), respectively. At B 1.7+/-0.4mm (22%) versus 2.0+/-0.4mm (25%), at C 1.7+/-0.4mm (22%) versus 2.2+/-0.4mm (27%) at D 2.0+/-0.4mm (25%) versus 2.4+/-0.5mm (30%) and at E 2.2+/-0.3mm (27%) versus 2.6+/-0.3mm (32%). Mean orientation of the major axis was (A) 0.8+/-23.3 degrees , (B) 1.8+/-31.3 degrees , (C) 14.0+/-15.5 degrees , (D) -28.8+/-48.0 degrees and (E) 18.4+/-22.2 degrees. CONCLUSIONS: Aortic pulsatile distention in young healthy volunteers is asymmetric, with up to 41% radius change in the descending aorta. This study offers a frame of reference for dynamic imaging studies in patients with aortic pathology and provides a valuable non-invasive tool for future research into aortic distention, development and localization of vascular pathology.

Evaluation of Quality of Life Outcomes Following Palliative Treatment of Bone Metastases with Magnetic Resonance-guided High Intensity Focused Ultrasound: An International Multicentre Study.

AIMS: To determine quality of life (QoL) outcomes after palliation of pain from bone metastases using magnetic resonance-guided high intensity focused ultrasound (MR-guided HIFU), measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C15-PAL and the QLQ-BM22 questionnaires. MATERIALS AND METHODS: Twenty patients undergoing MR-guided HIFU in an international multicentre trial self-completed the QLQ-C15-PAL and QLQ-BM22 questionnaires before and on days 7, 14, 30, 60 and 90 post-treatment. Descriptive statistics were used to represent changes in symptom and functional scales over time and to determine their clinical significance. QoL changes were compared in pain responders and non-responders (who were classified according to change in worst pain score and analgesic intake, between baseline and day 30). RESULTS: Eighteen patients had analysable QoL data. Clinically significant improvements were seen in the QoL scales of physical functioning, fatigue, appetite loss, nausea and vomiting, constipation and pain in the 53% of patients who were classified as responders at day 30. No significant changes were seen in the 47% of patients who were non-responders at this time point. CONCLUSION: Local treatment of pain from bone metastases with MR-guided HIFU, even in the presence of disseminated malignancy, has a substantial positive effect on physical functioning, and improves other symptomatic QoL measures. This indicated a greater response to treatment over and above pain control alone. MR-guided HIFU is non-invasive and should be considered for patients with localised metastatic bone pain and poor QoL.

Development and testing of passive tracking markers for different field strengths and tracking speeds.

Susceptibility markers for passive tracking need to be small in order to maintain the shape and mechanical properties of the endovascular device. Nevertheless, they also must have a high magnetic moment to induce an adequate artefact at a variety of scan techniques, tracking speeds and, preferably, field strengths. Paramagnetic markers do not satisfy all of these requirements. Ferro- and ferrimagnetic materials were therefore investigated with a vibrating sample magnetometer and compared with the strongly paramagnetic dysprosium oxide. Results indicated that the magnetic behaviour of stainless steel type AISI 410 corresponds the best with ideal marker properties. Markers with different magnetic moments were constructed and tested in in vitro and in vivo experiments. The appearance of the corresponding artefacts was field strength independent above magnetic saturation of 1.5 T. Generally, the contrast-to-noise ratio decreased at increasing tracking speed and decreasing magnetic moment. Device depiction was most consistent at a frame rate of 20 frames per second.

Spatial distribution of oil depots monitored in human muscle using MRI.

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. According to mass transport models, the drug-release rate from these injections is determined by the surface area of the oil depot. Until now, the size of the surface area of injected depots has not been assessed, however. MRI provides an excellent possibility to distinguish between water and adipose tissue. The aim of this study was to investigate whether MRI can be used to determine the shape and hence the surface area of oil depots in muscle tissue. The developed MRI-scan protocol is demonstrated to be suitable for visualising oil depots. It was applied to determine the surface area of 0.5mL oil, i.m. injected in healthy volunteers. The mean (±RSD) surface area and volume of the depots recovered after injection was 755.4mm(2) (±26.5) and 520.1mm(3) (±24.6). It is shown that the depot disappearance from the injection site is very variable between volunteers. It is suggested that the oil is first solubilized and subsequently distributed. In all cases, the oil was not detectable after 14days. These factors are relevant for the understanding of the mechanism by which compounds are released out of oil depots.

Intercostal high intensity focused ultrasound for liver ablation: The influence of beam shaping on sonication efficacy and near-field risks.

PURPOSE: One of the major issues in high intensity focused ultrasound ablation of abdominal lesions is obstruction of the ultrasound beam by the thoracic cage. Beam shaping strategies have been shown by several authors to increase focal point intensity while limiting rib exposure. However, as rib obstruction leaves only part of the aperture available for energy transmission, conserving total emitted acoustic power, the intensity in the near-field tissues inherently increases after beam shaping. Despite of effective rib sparing, those tissues are therefore subjected to increased risk of thermal damage. In this study, for a number of clinically representative intercostal sonication geometries, modeling clinically available hardware, the effect of beam shaping on both the exposure of the ribs and near-field to acoustic energy was evaluated and the implications for the volumetric ablation rate were addressed. METHODS: A relationship between rib temperature rise and acoustic energy density was established by means of in vivo MR thermometry and simulations of the incident acoustic energy for the corresponding anatomies. This relationship was used for interpretation of rib exposure in subsequent numerical simulations in which rib spacing, focal point placement, and the focal point trajectory were varied. The time required to heat a targeted region to 65 °C was determined without and with the application of beam shaping. The required sonication time was used to calculate the acoustic energy density at the fat-muscle interface and at the surface of the ribs. At the fat-muscle interface, exposure was compared to available literature data and rib exposure was interpreted based on the earlier obtained relation between measured temperature rise and simulated acoustic energy density. To estimate the volumetric ablation rate, the cool-down time between periods of energy exposure was estimated using a time-averaged power limit of 100 kJ/h. RESULTS: At the level of the ribs, the temperature rise-energy density proportionality constant was estimated to be 6.0-7.6 °C/(J/mm(2)). Beam shaping by the geometric shadow method typically reduces the acoustic intensity a factor of 2, considering the 1 cm(2) with the highest exposure. For a 4 mm diameter circular sonication trajectory, the near-field energy limit of 2.5 J/mm(2) was exceeded for all considered geometries. The estimated rib temperature was in all but one (sonication 50 mm behind the ribs, with 15 mm rib spacing and a 4 mm diameter circular sonication trajectory) of the considered scenarios within acceptable limits. For those sonication scenarios where a single sonication is considered safe both in terms of near-field as well as rib heating, volumetric ablation rates in the order of 1 ml/h are estimated. CONCLUSIONS: Intercostal sonication is associated with an increased risk of near-field overheating. This risk is strongly dependent on the considered rib spacing, the placement of the focus behind the ribs, and the selected sonication trajectory. For the hardware under simulation, obstruction by the thoracic cage renders ablations of clinically relevant volumes within a practical time-frame unfeasible in a large part of the liver. Improvements maybe expected from transducer designs with a larger active surface and/or nonlinear sonication strategies.