Reluctantly abandoning my career in rock-and-roll and inspired by the elegant mathematics of reconstruction in computed tomography I started working in medical imaging as a clinical scientist. Working in the clinical environment I appreciated how much in medicine was unknown. I became convinced that a physics and engineering approach could contribute to improving healthcare and that this must be done in close collaboration with clinical colleagues in order to be relevant. I also became convinced that real impact in healthcare engineering would only come about by working closely with industry. Only this would enable wide dissemination.

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent.

This chapter summarizes image analysis and biomechanical modeling of the breast that has been directed to applications in surgery and, in particular, oncoplastic surgical planning. A key component of such applications is the ability to model deformation of the breast between the patient standing, with the breast unsupported, and lying prone, for MR imaging, and lying supine, for surgery. We summarize the state-of-the-art and describe our approach to computing the unloaded (gravity free) configuration of the breast from prone and supine MR or CT images and how we use that to compute the transformation from prone to supine to standing positions. We also outline our approach to estimating the impact of oncoplastic surgery and surgical recovery on breast shape.

The COVID-19 pandemic has been a great challenge to healthcare systems worldwide. It highlighted the need for robust predictive models which can be readily deployed to uncover heterogeneities in disease course, aid decision-making and prioritise treatment. We adapted an unsupervised data-driven model-SuStaIn, to be utilised for short-term infectious disease like COVID-19, based on 11 commonly recorded clinical measures. We used 1344 patients from the National COVID-19 Chest Imaging Database (NCCID), hospitalised for RT-PCR confirmed COVID-19 disease, splitting them equally into a training and an independent validation cohort. We discovered three COVID-19 subtypes (General Haemodynamic, Renal and Immunological) and introduced disease severity stages, both of which were predictive of distinct risks of in-hospital mortality or escalation of treatment, when analysed using Cox Proportional Hazards models. A low-risk Normal-appearing subtype was also discovered. The model and our full pipeline are available online and can be adapted for future outbreaks of COVID-19 or other infectious disease.

Augmented Reality (AR) is considered to be a promising technology for the guidance of laparoscopic liver surgery. By overlaying pre-operative 3D information of the liver and internal blood vessels on the laparoscopic view, surgeons can better understand the location of critical structures. In an effort to enable AR, several authors have focused on the development of methods to obtain an accurate alignment between the laparoscopic video image and the pre-operative 3D data of the liver, without assessing the benefit that the resulting overlay can provide during surgery. In this paper, we present a study that aims to assess quantitatively and qualitatively the value of an AR overlay in laparoscopic surgery during a simulated surgical task on a phantom setup. We design a study where participants are asked to physically localise pre-operative tumours in a liver phantom using three image guidance conditions - a baseline condition without any image guidance, a condition where the 3D surfaces of the liver are aligned to the video and displayed on a black background, and a condition where video see-through AR is displayed on the laparoscopic video. Using data collected from a cohort of 24 participants which include 12 surgeons, we observe that compared to the baseline, AR decreases the median localisation error of surgeons on non-peripheral targets from 25.8 mm to 9.2 mm. Using subjective feedback, we also identify that AR introduces usability improvements in the surgical task and increases the perceived confidence of the users. Between the two tested displays, the majority of participants preferred to use the AR overlay instead of navigated view of the 3D surfaces on a separate screen. We conclude that AR has the potential to improve performance and decision making in laparoscopic surgery, and that improvements in overlay alignment accuracy and depth perception should be pursued in the future.

The study of rigid body dynamics in soft tissue is an essential part of orthopaedic imaging. Our focus is the foot and ankle structure, which consists of 28 bones surrounded by a variety of soft tissue such as 30 muscles, numerous ligaments, bursae and nerves. The importance of understanding the involved dynamics is evident by the frequent need to find functional joint replacements to fight diseases such as hindfoot arthritis. We study a simplified problem by constructing a phantom with two ”bones” submerged in silicone and a remotely controlled LEGO robot that moves one of the two bones. We perform motion registration by manipulating the bone segmented from an initial static scan and matching its digitally reconstructed radiographs to a sequence of scanned X-ray projections. The registration of the 3D volume to 2D projections requires the right combination of optimization and interpolation to achieve an optimal result. We test four different approaches with the help of the Flexible Algorithms for Image Registration (FAIR) toolbox.

ContextAs the role of AI in healthcare continues to expand there is increasing awareness of the potential pitfalls of AI and the need for guidance to avoid them.ObjectivesTo provide ethical guidance on developing narrow AI applications for surgical training curricula. We define standardised approaches to developing AI driven applications in surgical training that address current recognised ethical implications of utilising AI on surgical data. We aim to describe an ethical approach based on the current evidence, understanding of AI and available technologies, by seeking consensus from an expert committee.Evidence acquisitionThe project was carried out in 3 phases: (1) A steering group was formed to review the literature and summarize current evidence. (2) A larger expert panel convened and discussed the ethical implications of AI application based on the current evidence. A survey was created, with input from panel members. (3) Thirdly, panel-based consensus findings were determined using an online Delphi process to formulate guidance. 30 experts in AI implementation and/or training including clinicians, academics and industry contributed. The Delphi process underwent 3 rounds. Additions to the second and third-round surveys were formulated based on the answers and comments from previous rounds. Consensus opinion was defined as ≥ 80% agreement.Evidence synthesisThere was 100% response from all 3 rounds. The resulting formulated guidance showed good internal consistency, with a Cronbach alpha of >0.8. There was 100% consensus that there is currently a lack of guidance on the utilisation of AI in the setting of robotic surgical training. Consensus was reached in multiple areas, including: 1. Data protection and privacy; 2. Reproducibility and transparency; 3. Predictive analytics; 4. Inherent biases; 5. Areas of training most likely to benefit from AI.ConclusionsUsing the Delphi methodology, we achieved international consensus among experts to develop and reach content validation for guidance on ethical implications of AI in surgical training. Providing an ethical foundation for launching narrow AI applications in surgical training. This guidance will require further validation.Patient summaryAs the role of AI in healthcare continues to expand there is increasing awareness of the potential pitfalls of AI and the need for guidance to avoid them.In this paper we provide guidance on ethical implications of AI in surgical training.

Aims and Objectives: To investigate differences in airway morphology on computed tomography (CT) imaging in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy subjects. Methods: Airway segmentations were derived from CT scans in 14 IPF patients and 14 healthy subjects and examined using AirQuant, an open-source software tool. Diameters and lengths of airway segments (representing an airway between branching or endpoints) were measured. These were used to derive the median intertapering (change in average segment diameter compared to parent) and tortuosity (ratio of actual length to Euclidean length) for all central (generations 2-6) and distal (beyond 6) airway segments in the upper and lower lobes. Medians were compared between IPF and healthy using the Mann-Whitney-U test. Results: IPF patients: mean age=63 years; 93% male; mean DLco=49%. Healthy subjects had normal lung function tests. Significant differences in segmental intertapering (p<0.0001) and tortuosity (p<0.0001) between IPF and healthy subjects were most marked in the lower lobes (Figure 1). Increased segmental airway dilatation (p<0.01) and tortuosity (p<0.01) were observed in upper lobe central airways in IPF compared to healthy subjects. Conclusions: Quantitative measures of airway tapering are reduced and airway tortuosity increased in IPF compared to healthy subjects. Airway abnormalities are evident in proximal IPF airways, particularly in the lower lobes.

Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. Conclusions: The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.

PURPOSE:The initial registration of a 3D pre-operative CT model to a 2D laparoscopic video image in augmented reality systems for liver surgery needs to be fast, intuitive to perform and with minimal interruptions to the surgical intervention. Several recent methods have focussed on using easily recognisable landmarks across modalities. However, these methods still need manual annotation or manual alignment. We propose a novel, fully automatic pipeline for 3D-2D global registration in laparoscopic liver interventions.METHODS:Firstly, we train a fully convolutional network for the semantic detection of liver contours in laparoscopic images. Secondly, we propose a novel contour-based global registration algorithm to estimate the camera pose without any manual input during surgery. The contours used are the anterior ridge and the silhouette of the liver.RESULTS:We show excellent generalisation of the semantic contour detection on test data from 8 clinical cases. In quantitative experiments, the proposed contour-based registration can successfully estimate a global alignment with as little as 30% of the liver surface, a visibility ratio which is characteristic of laparoscopic interventions. Moreover, the proposed pipeline showed very promising results in clinical data from 5 laparoscopic interventions.CONCLUSIONS:Our proposed automatic global registration could make augmented reality systems more intuitive and usable for surgeons and easier to translate to operating rooms. Yet, as the liver is deformed significantly during surgery, it will be very beneficial to incorporate deformation into our method for more accurate registration.

We describe a novel, two-stage computer assistance system for lung anomaly detection using ultrasound imaging in the intensive care setting to improve operator performance and patient stratification during coronavirus pandemics. The proposed system consists of two deep-learning-based models: a quality assessment module that automates predictions of image quality, and a diagnosis assistance module that determines the likelihood-of-anomaly in ultrasound images of sufficient quality. Our two-stage strategy uses a novelty detection algorithm to address the lack of control cases available for training the quality assessment classifier. The diagnosis assistance module can then be trained with data that are deemed of sufficient quality, guaranteed by the closed-loop feedback mechanism from the quality assessment module. Using more than 25,000 ultrasound images from 37 COVID-19-positive patients scanned at two hospitals, plus 12 control cases, this study demonstrates the feasibility of using the proposed machine learning approach. We report an accuracy of 86% when classifying between sufficient and insufficient quality images by the quality assessment module. For data of sufficient quality - as determined by the quality assessment module - the mean classification accuracy, sensitivity, and specificity in detecting COVID-19-positive cases were 0.95, 0.91, and 0.97, respectively, across five holdout test data sets unseen during the training of any networks within the proposed system. Overall, the integration of the two modules yields accurate, fast, and practical acquisition guidance and diagnostic assistance for patients with suspected respiratory conditions at point-of-care.

BACKGROUND:Compared to open surgery, minimally invasive liver resection has improved short term outcomes. It is however technically more challenging. Navigated image guidance systems (IGS) are being developed to overcome these challenges. The aim of this systematic review is to provide an overview of their current capabilities and limitations. METHODS:Medline, Embase and Cochrane databases were searched using free text terms and corresponding controlled vocabulary. Titles and abstracts of retrieved articles were screened for inclusion criteria. Due to the heterogeneity of the retrieved data it was not possible to conduct a meta-analysis. Therefore results are presented in tabulated and narrative format. RESULTS:Out of 2015 articles, 17 pre-clinical and 33 clinical papers met inclusion criteria. Data from 24 articles that reported on accuracy indicates that in recent years navigation accuracy has been in the range of 8-15 mm. Due to discrepancies in evaluation methods it is difficult to compare accuracy metrics between different systems. Surgeon feedback suggests that current state of the art IGS may be useful as a supplementary navigation tool, especially in small liver lesions that are difficult to locate. They are however not able to reliably localise all relevant anatomical structures. Only one article investigated IGS impact on clinical outcomes. CONCLUSIONS:Further improvements in navigation accuracy are needed to enable reliable visualisation of tumour margins with the precision required for oncological resections. To enhance comparability between different IGS it is crucial to find a consensus on the assessment of navigation accuracy as a minimum reporting standard.

An MR-Linac can provide motion information of tumour and organs-at-risk before, during, and after beam delivery. However, MR imaging cannot provide real-time high-quality volumetric images which capture breath-to-breath variability of respiratory motion. Surrogate-driven motion models relate the motion of the internal anatomy to surrogate signals, thus can estimate the 3D internal motion from these signals. Internal surrogate signals based on patient anatomy can be extracted from 2D cine-MR images, which can be acquired on an MR-Linac during treatment, to build and drive motion models. In this paper we investigate different MRI-derived surrogate signals, including signals generated by applying principal component analysis to the image intensities, or control point displacements derived from deformable registration of the 2D cine-MR images. We assessed the suitability of the signals to build models that can estimate the motion of the internal anatomy, including sliding motion and breath-to-breath variability. We quantitatively evaluated the models by estimating the 2D motion in sagittal and coronal slices of 8 lung cancer patients, and comparing them to motion measurements obtained from image registration. For sagittal slices, using the first and second principal components on the control point displacements as surrogate signals resulted in the highest model accuracy, with a mean error over patients around 0.80 mm which was lower than the in-plane resolution. For coronal slices, all investigated signals except the skin signal produced mean errors over patients around 1 mm. These results demonstrate that surrogate signals derived from 2D cine-MR images, including those generated by applying principal component analysis to the image intensities or control point displacements, can accurately model the motion of the internal anatomy within a single sagittal or coronal slice. This implies the signals should also be suitable for modelling the 3D respiratory motion of the internal anatomy.

Background The laparoscopic approach to liver resection may reduce morbidity and hospital stay. However, uptake has been slow due to concerns about patient safety and oncological radicality. Image guidance systems may improve patient safety by enabling 3D visualisation of critical intra- and extrahepatic structures. Current systems suffer from non-intuitive visualisation and a complicated setup process. A novel image guidance system (SmartLiver), offering augmented reality visualisation and semi-automatic registration has been developed to address these issues. A clinical feasibility study evaluated the performance and usability of SmartLiver with either manual or semi-automatic registration. Methods Intraoperative image guidance data were recorded and analysed in patients undergoing laparoscopic liver resection or cancer staging. Stereoscopic surface reconstruction and iterative closest point matching facilitated semi-automatic registration. The primary endpoint was defined as successful registration as determined by the operating surgeon. Secondary endpoints were system usability as assessed by a surgeon questionnaire and comparison of manual vs. semi-automatic registration accuracy. Since SmartLiver is still in development no attempt was made to evaluate its impact on perioperative outcomes. Results The primary endpoint was achieved in 16 out of 18 patients. Initially semi-automatic registration failed because the IGS could not distinguish the liver surface from surrounding structures. Implementation of a deep learning algorithm enabled the IGS to overcome this issue and facilitate semi-automatic registration. Mean registration accuracy was 10.9 ± 4.2 mm (manual) vs. 13.9 ± 4.4 mm (semi-automatic) (Mean difference − 3 mm; p = 0.158). Surgeon feedback was positive about IGS handling and improved intraoperative orientation but also highlighted the need for a simpler setup process and better integration with laparoscopic ultrasound. Conclusion The technical feasibility of using SmartLiver intraoperatively has been demonstrated. With further improvements semi-automatic registration may enhance user friendliness and workflow of SmartLiver. Manual and semi-automatic registration accuracy were comparable but evaluation on a larger patient cohort is required to confirm these findings.

Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery. In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation. We included 51 from a total of 5,047 articles which met all our inclusion criteria. We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies. Conclusions were weighted towards higher-quality articles. We identified a total of 36 thoracic imaging features studied at exacerbation of COPD. Studies were generally heterogeneous in their measurements and focus. Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations. An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension. Most information was gained from CT studies. We present the first ever composite imaging signature of COPD exacerbations. While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response.

The attention and resources of AI researchers have been captured by COVID-19. However, successful adoption of AI models in the fight against the pandemic is facing various challenges, including moving clinical needs as the epidemic progresses and the necessity to translate models to local healthcare situations.

The foot and ankle is a complex structure consisting of 28 bones and 30 joints that changes from being completely mobile when positioning the foot on the floor to a rigid closed pack position during propulsion such as when running or jumping. An understanding of this complex structure has largely been derived from cadaveric studies. In vivo studies have largely relied on skin surface markers and multi-camera systems that are unable to differentiate small motions between the bones of the foot. MRI and CT based studies have struggled to interpret functional weight bearing motion as imaging is largely static and non-load bearing. Arthritic diseases of the foot and ankle are treated either by fusion of the joints to remove motion, or joint replacement to retain motion. Until a better understanding of the biomechanics of these joints can be achieved.

The VERDICT framework for modelling diffusion MRI data aims to relate parameters from a biophysical model to histological features used for tumour grading in prostate cancer. Validation of the VERDICT model is necessary for clinical use. This study compared VERDICT parameters obtained ex vivo with histology in five specimens from radical prostatectomy. A patient-specific 3D-printed mould was used to investigate the effects of fixation on VERDICT parameters and to aid registration to histology. A rich diffusion data set was acquired in each ex vivo prostate before and after fixation. At both time points, data were best described by a two-compartment model: the model assumes that an anisotropic tensor compartment represents the extracellular space and a restricted sphere compartment models the intracellular space. The effect of fixation on model parameters associated with tissue microstructure was small. The patient-specific mould minimized tissue deformations and co-localized slices, so that rigid registration of MRI to histology images allowed region-based comparison with histology. The VERDICT estimate of the intracellular volume fraction corresponded to histological indicators of cellular fraction, including high values in tumour regions. The average sphere radius from VERDICT, representing the average cell size, was relatively uniform across samples. The primary diffusion direction from the extracellular compartment of the VERDICT model aligned with collagen fibre patterns in the stroma obtained by structure tensor analysis. This confirmed the biophysical relationship between ex vivo VERDICT parameters and tissue microstructure from histology.

We propose a pipeline to acquire a scalar tapering measurement from the carina to the most distal point of an individual airway visible on computed tomography (CT). We show the applicability of using tapering measurements on clinically acquired data by quantifying the reproducibility of the tapering measure. We generate a spline from the centerline of an airway to measure the area and arclength at contiguous intervals. The tapering measurement is the gradient of the linear regression between area in log space and arclength. The reproducibility of the measure was assessed by analyzing different radiation doses, voxel sizes, and reconstruction kernel on single timepoint and longitudinal CT scans and by evaluating the effect of airway bifurcations. Using 74 airways from 10 CT scans, we show a statistical difference, p = 3.4 × 10 - 4 , in tapering between healthy airways ( n = 35 ) and those affected by bronchiectasis ( n = 39 ). The difference between the mean of the two populations is 0.011    mm - 1 , and the difference between the medians of the two populations was 0.006    mm - 1 . The tapering measurement retained a 95% confidence interval of ± 0.005    mm - 1 in a simulated 25 mAs scan and retained a 95% confidence of ± 0.005    mm - 1 on simulated CTs up to 1.5 times the original voxel size. We have established an estimate of the precision of the tapering measurement and estimated the effect on precision of the simulated voxel size and CT scan dose. We recommend that the scanner calibration be undertaken with the phantoms as described, on the specific CT scanner, radiation dose, and reconstruction algorithm that are to be used in any quantitative studies.