OBJECTIVE:Prior imaging studies have suggested that monosodium urate (MSU) crystal deposits in joints dissolve more rapidly than those in tendons during urate-lowering therapy (ULT) for gout. This study aimed to examine whether urate deposits visible on dual-energy computed tomography (DECT) reduce at different rates in joints and tendons during ULT. METHODS:Participants with gout from 2 clinical trials of oral ULT with the following criteria were included: paired DECT scans of the feet and ankles over 1-year of ULT, first DECT scan showing total urate volume ≥ 0.5 cm3, second DECT scan showing reduced total urate volume, and DECT deposition visible in at least 1 joint and 1 tendon on the first scan. DECT urate volumes in up to 3 index joints and up to 3 index tendons at baseline and year 1 were measured in known order. Data were analyzed using a general linear mixed analysis of covariance. RESULTS:In total, 125 joint deposits and 95 tendon deposits were analyzed from 50 participants. The least means change (95% CI) in DECT urate volumes of the joint deposits was -0.37 (-0.47 to -0.26) cm3 and of the tendon deposits was -0.39 (-0.50 to -0.27) cm3 (both P < 0.001). There was no difference in the change in DECT urate volumes between the joint and tendon deposits; least means difference was 0.02 (95% CI -0.09 to 0.13) cm3 (P = 0.73). CONCLUSION:This DECT study indicates that similar rates of MSU crystal dissolution occur at both joints and tendons during oral ULT.

OBJECTIVES:In gout, MSU crystal deposition occurs preferentially within certain joints, particularly the first MTP joint. The aim of this study was to map the distribution of MSU crystals within the MTP joints in people with tophaceous gout. METHODS:Bilateral foot dual-energy CT (DECT) scans of 119 people with tophaceous gout were analysed. Each quadrant (dorsal, plantar, medial and lateral) of the metatarsal head and phalangeal base was scored independently by two trained readers for MSU crystal deposition (9696 sites scored). MSU crystal deposition was considered present if crystals were in contact with or directly adjacent (within 1 mm) to bone or cartilage. Data were analysed using general estimating equations. RESULTS:MSU crystal deposition was most frequent at the medial quadrant of the first metatarsal head (60%) followed by the plantar quadrants of the first and second metatarsal heads and medial quadrant of the first phalangeal base (all >30%). The phalangeal bases of the third and fourth MTP joints were rarely affected, particularly the lateral quadrants (1%). Across all joints, there was more MSU crystal deposition at the first MTP joint compared with other joints, at the metatarsal head compared with the phalangeal base, and at the plantar and medial quadrants compared with other quadrants (P < 0.0001 for all comparisons). CONCLUSION:In people with tophaceous gout, MSU crystal deposition is unevenly distributed. There is marked variation in sites of deposition not only between different MTP joints, but also within these joints.

In breast surgical planning, accurate registration of MR images across patient positions has the potential to improve the localisation of tumours during breast cancer treatment. While learning-based registration methods have recently become the state-of-the-art approach for most medical image registration tasks, these methods have yet to make inroads into breast image registration due to certain difficulties-the lack of rich texture information in breast MR images and the need for the deformations to be diffeomophic. In this work, we propose learning strategies for breast MR image registration that are amenable to diffeomorphic constraints, together with early experimental results from in-silico and in-vivo experiments. One key contribution of this work is a registration network which produces superior registration outcomes for breast images in addition to providing diffeomorphic guarantees.

Background: Predicting breast tissue motion using biomechanical models can provide navigational guidance during breast cancer treatment procedures. These models typically do not account for changes in posture between procedures. Difference in shoulder position can alter the shape of the pectoral muscles and breast. A greater understanding of the differences in the shoulder orientation between prone and supine could improve the accuracy of breast biomechanical models. Methods: 19 landmarks were placed on the sternum, clavicle, scapula, and humerus of the shoulder girdle in prone and supine breast MRIs (N = 10). These landmarks were used in an optimization framework to fit subjectspecific skeletal models and compare joint angles of the shoulder girdle between these positions. Findings: The mean Euclidean distance between joint locations from the fitted skeletal model and the manually identified joint locations was 15.7 mm 2.7 mm. Significant differences were observed between prone and supine. Compared to supine position, the shoulder girdle in the prone position had the lateral end of the clavicle in more anterior translation (i.e., scapula more protracted) (P < 0.05), the scapula in more protraction (P < 0.01), the scapula in more upward rotation (associated with humerus elevation) (P < 0.05); and the humerus more elevated (P < 0.05) for both the left and right sides. Interpretation: Shoulder girdle orientation was found to be different between prone and supine. These differences would affect the shape of multiple pectoral muscles, which would affect breast shape and the accuracy of biomechanical models.

INTRODUCTION:There is an increasing incidence of hip and pelvic fractures with an ageing population. Accurate and timely diagnosis is important in the emergency setting. While magnetic resonance imaging (MRI) is the gold standard, it is a limited resource. Dual energy CT (DECT) is comparable to MRI in detection of bone marrow oedema. Our hospital was the first centre in our country to introduce DECT for occult pelvic fractures. We aimed to describe its utility in occult pelvic fractures since commencement. METHODS:Retrospective study of consecutive pelvic bone CT (conventional or DECT) performed to look for an occult fracture over a 10-month period. Sensitivity and specificity calculated based on clinical and imaging follow-up. ROC study performed where three observers visually interpreted pelvic radiographs, conventional CT and DECT and scored their confidence for an acute fracture from 1 to 5. The null hypothesis was that DECT would not improve observer performance compared with conventional CT. RESULTS:DECT studies were performed on 178 patients of whom 84 (47%) had acute fractures. Sensitivity on audit was 99% and specificity was 100%. ROC analysis showed that, for all observers, the area under curve increased from radiograph to conventional CT to DECT. The difference between conventional CT and DECT was statistically significant for all observers where metal implants were not present. CONCLUSION:DECT improves accuracy compared to conventional CT in the diagnosis of occult pelvic fractures and should be used for this indication when available.

Objectives The dynamics of monosodium urate (MSU) crystal changes across a range of serum urate concentrations in people with gout are unknown. This study aimed to systematically examine the relationship between serum urate and changes in dual-energy CT (DECT) urate volume in people with gout and stable serum urate concentrations. Methods Individual participant data were analysed from three studies of people with gout. The time periods for the analysis were selected to identify study participants with serial DECT scans of both feet over a 12-month epoch of stable urate-lowering therapy and serum urate concentrations. Data from 251 study participants were analysed using a mixed models analysis of covariance approach according to mean serum urate cut-points and mean serum urate bands. Results For all mean serum urate cut-points assessed (0.24, 0.30, 0.36, 0.42 and 0.48 mmol/L), reductions in DECT urate volumes were observed below the cut-point. Increased DECT urate volumes were observed at or above the 0.48 mmol/L mean serum urate cut-point. Differences in the change in DECT volume were observed for the 0.42 mmol/L cut-point (p=0.0044) and the 0.48 mmol/L cut-point (p<0.0001). Significantly reduced DECT urate volumes were observed for the mean serum urate bands<0.24 mmol/L and 0.24-0.29 mmol/L and increased DECT urate volume was observed for the mean serum urate band >= 0.48 mmol/L. Conclusions Over 1 year, MSU crystal dissolution, as measured by DECT, occurs with mean serum urate bands of<0.24 mmol/L and 0.24-0.29 mmol/L while MSU crystal formation occurs with mean serum urate >= 0.48 mmol/L.

Objective. This study aimed to identify variables that predict gout remission in people with erosive gout receiving urate-lowering therapy. Methods. We analyzed data from a two-year, double-masked randomized-controlled trial of people with erosive gout, randomized to a serum urate target of <0.20 mmol/L or <0.30 mmol/L using oral urate-lowering therapies. All participants had dual-energy computed tomography (DECT) scans of the feet and ankles at baseline. The proportion of participants achieving gout remission according to the 2016 preliminary gout remission criteria and simplified gout remission criteria (without the patient reported outcomes) was analyzed. Logistic regression models were used to evaluate predictors of gout remission in year 2. Results. The preliminary gout remission criteria were fulfilled in 11 of 97 participants (11%) at year 1 and 21 of 92 participants (23%) at year 2. The simplified criteria were fulfilled in 26 of 97 participants (27%) in year 1 and 40 of 92 participants (44%) in year 2. In multivariable regression models, baseline DECT monosodium urate crystal volume was the only significant independent predictor of gout remission at year 2, using either criteria. Each 1-cm(3) increase in the baseline DECT monosodium urate crystal volume decreased the odds of fulfilling the 2016 preliminary gout remission criteria (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.46-0.93; P = 0.02) and the simplified gout remission criteria (OR 0.57, 95% CI 0.41-0.78; P < 0.001). Conclusion. In people with erosive gout on urate-lowering therapy, higher baseline DECT monosodium urate crystal volume is associated with lower odds of gout remission after two years of treatment, defined by either the preliminary gout remission criteria or simplified gout remission criteria.

INTRODUCTION:Primary objective was to investigate the prevalence of ossification of the posterior longitudinal ligament (OPLL) in a mixed demographic region, especially in the Pacific Island population. Secondary objective was to investigate the prevalence of diabetes mellitus and cervical diffuse skeletal hyperostosis (DISH) in patients with and without OPLL. METHODS:Using the local picture archiving and communication system (PACS), cervical spine computed tomography (CT) examinations over a 2-month period were retrospectively assessed for the presence of OPLL. Basic demographic data were recorded-gender, age, ethnicity, presence of cervical DISH and the presence or absence of diabetes mellitus. RESULTS:A total of 1692 CT examinations were included in the study. The distribution of the ethnic groups was 57.3% European, 12.09% Pacific peoples, 11.9% Māori, 11.53% Asian, 0.95% Middle Eastern/Latin American/African and 6.3% not specified. Overall, 47 cases of OPPL were identified (2.78%). The prevalence of OPPL in the Pacific ethnic groups was significantly higher than the European ethnic group 8.4% versus 0.6%, P < 0.05. The prevalence of OPLL was also significantly higher in the Asian (6.9%) and Māori (3.6%) than in the European ethnic group, P < 0.05. A significantly higher proportion of the patients with OPLL had underlying diabetes 20/47 (42.6%) compared with the study population 196/1692 (11.6%), P < 0.05. Seven cases of OPPL (14.9%) had associated cervical DISH, which was significantly higher compared with the study group (23/1692), P < 0.05. Using the Japanese Ministry of Health and Welfare classification system4, segmental type was the most common (34/47, 72.3%), followed by mixed (14.9%) and continuous types (12.8%). CONCLUSION:The prevalence of OPLL is significantly higher among the Pacific populations in Auckland. There is also increased prevalence in the Asian and Māori populations.

Clinical translation of personalised computational physiology workflows and digital twins can revolutionise healthcare by providing a better understanding of an individual's physiological processes and any changes that could lead to serious health consequences. However, the lack of common infrastructure for developing these workflows and digital twins has hampered the realisation of this vision. The Auckland Bioengineering Institute’s 12 LABOURS project aims to address these challenges by developing a Digital Twin Platform to enable researchers to develop and personalise computational physiology models to an individual’s health data in clinical workflows. This will allow clinical trials to be more efficiently conducted to demonstrate the efficacy of these personalised clinical workflows. We present a demonstration of the platform's capabilities using publicly available data and an existing automated computational physiology workflow developed to assist clinicians with diagnosing and treating breast cancer. We also demonstrate how the platform facilitates the discovery and exploration of data and the presentation of workflow results as part of clinical reports through a web portal. Future developments will involve integrating the platform with health systems and remote-monitoring devices such as wearables and implantables to support home-based healthcare. Integrating outputs from multiple workflows that are applied to the same individual's health data will also enable the generation of their personalised digital twin.Clinical Relevance— The proposed 12 LABOURS Digital Twin Platform will enable researchers to 1) more efficiently conduct clinical trials to assess the efficacy of their computational physiology workflows and support the clinical translation of their research; 2) reuse primary and derived data from these workflows to generate novel workflows; and 3) generate personalised digital twins by integrating the outputs of different computational physiology workflows.

ObjectiveImage-guided biopsy is well-established in the diagnosis of musculoskeletal lesions. While several studies have demonstrated a high diagnostic yield in image-guided biopsy, there are no current guidelines around procedural factors such as number of cores. Furthermore, there have been mixed results regarding which lesions are more favourable to a diagnostic biopsy. We wanted to evaluate diagnostic yield and concordance for image-guided biopsies for musculoskeletal lesions. The null hypothesis was that there are no controllable factors that contribute to positive yield.Materials and methodsRetrospective review of consecutive patients who underwent image-guided biopsy at a large teaching hospital for musculoskeletal lesions discussed at the sarcoma multi-disciplinary meeting. The formal biopsy histology report was evaluated, and biopsies were considered diagnostic or non-diagnostic. In those that had subsequent surgery (by wide excision or open biopsy), final and initial histology was compared and biopsies were considered concordant or not. Overall diagnostic yield and concordance were calculated. Statistical analysis was performed with Stata 13.0 (StataCorp).ResultsOver the 14-year period, 429 biopsies were included. Diagnostic yield was 85% and concordance was 100%. No cases of malignant lesions were initially called benign on biopsy. One biopsy had a complication (0.2%). Factors associated with higher diagnostic yield included soft tissue versus bone lesions, three or more cores and longer total specimen length. Factors that were not associated included core size, use of FNA cytology, gender, age, benign versus malignant, anatomic location and lesion appearance.ConclusionThe null hypothesis is rejected. The main predictor of diagnostic biopsy was total specimen length, independent of number of cores taken. Three or more cores and longer cores are optimal, though these factors are influenced by lesion biology and not always able to be controlled.

BACKGROUND:Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time.METHODS:Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout.RESULTS:No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes.CONCLUSIONS:Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time.

OBJECTIVE:The gouty tophus is an organized structure composed of monosodium urate (MSU) crystals and chronic inflammatory soft tissue. This dual-energy computed tomography (DECT) study aimed to determine whether the composition of the tophus changes during urate-lowering therapy.METHODS:Serial DECT scans from 32 people with gout were obtained over 2 years of allopurinol therapy, dose-escalated to serum urate of <0.36 mmoles/liter. Up to 5 index tophi were selected for each patient, with 103 separate tophi included in the analysis. Using manual outlining methods of conventional CT and DECT scans, the same index tophi were serially measured for total tophus volume and urate volume. For each tophus, the soft tissue volume was then calculated by subtracting the urate volume from the total tophus volume.RESULTS:The mean ± SD serum urate reduced from 0.43 ± 0.03 mmoles/liter at baseline to 0.31 ± 0.02 mmoles/liter at year 2. The mean ± SD total tophus volume reduced over the 2-year period from 5.17 ± 5.55 cm3 to 2.61 ± 2.73 cm3 (P < 0.0001). Greater reductions in tophus urate volumes than tophus soft tissue volumes were observed; the tophus urate volume decreased by 70.6%, and tophus soft tissue volume decreased by 37.8% (P < 0.0001). The mean tophus urate:soft tissue ratio reduced from 0.15 at baseline to 0.05 at year 2 (P < 0.001).CONCLUSION:The composition of the tophus is dynamic and changes during urate-lowering therapy for gout management. The soft tissue component of the tophus is slower to respond and may persist without measurable MSU crystal deposition.

Objectives In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy.Methods We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures.Results Improvements were observed in all tophus measures over the 2-year period. The mean (s.d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P < 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was -1.13 (-1.54, -0.71). The effect size (Cohen's d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71.Conclusion For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact.

OBJECTIVE:To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout.METHODS:We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points.RESULTS:Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups.CONCLUSION:Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout.

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Radiology is a key enabler of clinical activity and has been shown to be highly cost effective. Demand and activity have increased over time, with demand for computed tomography (CT), magnetic resource imaging (MRI) and ultrasound (US) growing faster than population growth. Complexity has also increased over time. Resources in the public sector have not kept up with demand, exacerbated by the COVID-19 pandemic. A reliance on an overseas trained workforce has resulted in critical shortages. Waiting times for CT, MRI and US across Aotearoa New Zealand remain well below targets and have not improved over 10 years. Robust links between clinical activity and radiology resourcing are needed to address the deficits and thereby maintain clinical safety.

Background Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout. Methods Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over 2 years from an additional 25 patients. Inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system). Results Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76–0.89) for sclerosis and 0.81 (0.72–0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements ( r = 0.65–0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90–0.98) for sclerosis score and 0.76 (0.65–0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores ( r = 0.87 and 0.71 respectively), but not with change in erosion scores over 2 years ( r = −0.04–0.15). Conclusion A semi-quantitative plain radiographic scoring method for the assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout.

Background/Purpose: Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion. Methods: Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate <= 5 mg/dL or 300 mu mol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function. Results: Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone). Conclusions: In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion. Published by Elsevier Inc.