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.

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.

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.

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.

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.

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.

Performance analysis of a dedicated breast MR-HIFU system for tumor ablation in breast cancer patients.

MR-guided HIFU ablation is a promising technique for the non-invasive treatment of breast cancer. A phase I study was performed to assess the safety and treatment accuracy and precision of MR-HIFU ablation in breast cancer patients (n=10) using a newly developed MR-HIFU platform dedicated to applications in the breast. In this paper a technical analysis of the performance of the dedicated breast MR-HIFU system during breast tumors ablation is described. The main points of investigation were the spatial targeting accuracy and precision of the system and the performance of real-time respiration-corrected MR thermometry.The mean targeting accuracy was in the range of 2.4-2.6 mm, whereas the mean targeting precision was in the range of 1.5-1.8 mm. To correct for respiration-induced magnetic field fluctuations during MR temperature mapping a look-up-table (LUT)-based correction method was used. An optimized procedural sedation protocol in combination with the LUT-based correction method allowed for precise MR thermometry during the ablation procedure (temperature standard deviation <3 °C). No unwanted heating in the near field (i.e. skin) nor in the far field (pectoral muscle) was detected.The newly developed dedicated breast MR-HIFU system allows for safe, accurate and precise ablation of breast tumors.

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.

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.

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.

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation of liver tumours.

Recent decades have seen a paradigm shift in the treatment of liver tumours from invasive surgical procedures to minimally invasive image-guided ablation techniques. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a novel, completely non-invasive ablation technique that has the potential to change the field of liver tumour ablation. The image guidance, using MR imaging and MR temperature mapping, provides excellent planning images and real-time temperature information during the ablation procedure. However, before clinical implementation of MR-HIFU for liver tumour ablation is feasible, several organ-specific challenges have to be addressed. In this review we discuss the MR-HIFU ablation technique, the liver-specific challenges for MR-HIFU tumour ablation, and the proposed solutions for clinical translation.

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.

Registration of 2D x-ray images to 3D MRI by generating pseudo-CT data.

Spatial and soft tissue information provided by magnetic resonance imaging can be very valuable during image-guided procedures, where usually only real-time two-dimensional (2D) x-ray images are available. Registration of 2D x-ray images to three-dimensional (3D) magnetic resonance imaging (MRI) data, acquired prior to the procedure, can provide optimal information to guide the procedure. However, registering x-ray images to MRI data is not a trivial task because of their fundamental difference in tissue contrast. This paper presents a technique that generates pseudo-computed tomography (CT) data from multi-spectral MRI acquisitions which is sufficiently similar to real CT data to enable registration of x-ray to MRI with comparable accuracy as registration of x-ray to CT. The method is based on a k-nearest-neighbors (kNN)-regression strategy which labels voxels of MRI data with CT Hounsfield Units. The regression method uses multi-spectral MRI intensities and intensity gradients as features to discriminate between various tissue types. The efficacy of using pseudo-CT data for registration of x-ray to MRI was tested on ex vivo animal data. 2D-3D registration experiments using CT and pseudo-CT data of multiple subjects were performed with a commonly used 2D-3D registration algorithm. On average, the median target registration error for registration of two x-ray images to MRI data was approximately 1 mm larger than for x-ray to CT registration. The authors have shown that pseudo-CT data generated from multi-spectral MRI facilitate registration of MRI to x-ray images. From the experiments it could be concluded that the accuracy achieved was comparable to that of registering x-ray images to CT data.

Vitamin D3 treatment of Crohn's disease patients increases stimulated T cell IL-6 production and proliferation.

BACKGROUND: Vitamin D3 has shown immune-modulating effects in CD4+ T cells from Crohn's disease patients in vitro. AIM: To investigate the effects of in vivo vitamin D3 treatment on T cells in Crohn's disease patients. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated at week 0 and at week 26 from 10 vitamin D3- and 10 placebo-treated Crohn's disease patients participating in a randomized, placebo-controlled, clinical trial study. Monocyte-depleted PBMC were stimulated with anti-CD3 and anti-CD28, and cultured for 7, days, to investigate CD4+ T-cell proliferation and T-cell cytokine production. RESULTS: In vitamin D3-treated patients, the median 25-hydroxyvitamin D3 levels increased 70 nmol/L compared with -5 nmol/L in the placebo group. Vitamin D3 treatment increased interleukin-6 production (delta = 188 pg/mL, range: -444 to 4071) compared with a decrease in the placebo group (delta = -896 pg/mL, range: -3841 to 1323) (P < 0.02, Wilcoxon rank sum test). Interestingly, vitamin D3 increased the amount of proliferating stimulated CD4+ T cells from median 41% (range: 10-75%) to 56% (range: 26-77%) (P = 0.02, Wilcoxon rank sum test). CONCLUSIONS: Vitamin D3 treatment of Crohn's disease patients increased the IL-6 levels. Interestingly, vitamin D3 treatment enhanced the CD4+ T cell proliferation.