Modern imaging of pituitary adenomas.

Decision-making in pituitary disease is critically dependent on high quality imaging of the sella and parasellar region. Magnetic resonance imaging (MRI) is the investigation of choice and, for the majority of patients, combined T1 and T2 weighted sequences provide the information required to allow surgery, radiotherapy (RT) and/or medical therapy to be planned and long-term outcomes to be monitored. However, in some cases standard clinical MR sequences are indeterminate and additional information is needed to help inform the choice of therapy for a pituitary adenoma (PA). This article reviews current recommendations for imaging of PA, examines the potential added value that alternative MR sequences and/or CT can offer, and considers how the use of functional/molecular imaging might allow definitive treatment to be recommended for a subset of patients who would otherwise be deemed unsuitable for (further) surgery and/or RT.Cambridge NIHR Biomedical Research Centr

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic

Methods of 3D printing models of pituitary tumors

Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Abstract: Background: Pituitary adenomas can give rise to a variety of clinical disorders and surgery is often the primary treatment option. However, preoperative magnetic resonance imaging (MRI) does not always reliably identify the site of an adenoma. In this setting molecular (functional) imaging (e.g. 11C-methionine PET/CT) may help with tumor localisation, although interpretation of these 2D images can be challenging. 3D printing of anatomical models for other indications has been shown to aid surgical planning and improve patient understanding of the planned procedure. Here, we explore the potential utility of four types of 3D printing using PET/CT and co-registered MRI for visualising pituitary adenomas. Methods: A 3D patient-specific model based on a challenging clinical case was created by segmenting the pituitary gland, pituitary adenoma, carotid arteries and bone using contemporary PET/CT and MR images. The 3D anatomical models were printed using VP, MEX, MJ and PBF 3D printing methods. Different anatomical structures were printed in color with the exception of the PBF anatomical model where a single color was used. The anatomical models were compared against the computer model to assess printing accuracy. Three groups of clinicians (endocrinologists, neurosurgeons and ENT surgeons) assessed the anatomical models for their potential clinical utility. Results: All of the printing techniques produced anatomical models which were spatially accurate, with the commercial printing techniques (MJ and PBF) and the consumer printing techniques (VP and MEX) demonstrating comparable findings (all techniques had mean spatial differences from the computer model of < 0.6 mm). The MJ, VP and MEX printing techniques yielded multicolored anatomical models, which the clinicians unanimously agreed would be preferable to use when talking to a patient; in contrast, 50%, 40% and 0% of endocrinologists, neurosurgeons and ENT surgeons respectively would consider using the PBF model. Conclusion: 3D anatomical models of pituitary tumors were successfully created from PET/CT and MRI using four different 3D printing techniques. However, the expert reviewers unanimously preferred the multicolor prints. Importantly, the consumer printers performed comparably to the commercial MJ printing technique, opening the possibility that these methods can be adopted into routine clinical practice with only a modest investment

Application of data fusion techniques and technologies for wearable health monitoring

Technological advances in sensors and communications have enabled discrete integration into everyday objects, both in the home and about the person. Information gathered by monitoring physiological, behavioural, and social aspects of our lives, can be used to achieve a positive impact on quality of life, health, and well-being. Wearable sensors are at the cusp of becoming truly pervasive, and could be woven into the clothes and accessories that we wear such that they become ubiquitous and transparent. To interpret the complex multidimensional information provided by these sensors, data fusion techniques are employed to provide a meaningful representation of the sensor outputs. This paper is intended to provide a short overview of data fusion techniques and algorithms that can be used to interpret wearable sensor data in the context of health monitoring applications. The application of these techniques are then described in the context of healthcare including activity and ambulatory monitoring, gait analysis, fall detection, and biometric monitoring. A snap-shot of current commercially available sensors is also provided, focusing on their sensing capability, and a commentary on the gaps that need to be bridged to bring research to market

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Exploring the role of molecular imaging in the diagnosis and management of primary adrenocortical disease

With the advent and evolution of modern imaging techniques, there has been an increase in the detection of adrenal lesions, most often incidentally (4–7% of all abdominal CT scans in patients >40 y). Computed tomography (CT) is generally preferred for the evaluation of adrenal masses, and often informs treatment decisions (e.g., surgical resection) by establishing lesion size, density and homogeneity. However, anatomical imaging provides limited or no information regarding the functional status of an adrenal mass, which is a key element in the decision-making process, particularly with respect to recommending surgery, and in guiding pre-, peri- and postoperative endocrine management. These challenges are exemplified by primary aldosteronism (PA), a condition caused by autonomous aldosterone secretion from one or both adrenal glands, and which accounts for between 5–14% of all hypertension. Distinguishing between unilateral and bilateral disease is a key step in the management pathway as it identifies those patients who might benefit from unilateral adrenalectomy to effect cure of biochemical hyperaldosteronism with reversal or amelioration of hypertension (± hypokalaemia). Adrenal vein sampling (AVS) remains the current gold standard for lateralisation (i.e. determining whether one or both adrenal glands are implicated). However, it is limited by its invasive nature and the requirement for an experienced interventional radiologist, given the challenges associated with successfully cannulating the right adrenal vein. Accordingly, alternative techniques for distinguishing unilateral and bilateral causes of PA have been proposed, including adrenal molecular imaging with the positron emission tomography radiotracer [11C]Metomidate (MTO PET). MTO has previously been shown to have high affinity for adrenocortical tissue (targeting the key enzymes CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase). This thesis examines the potential roles for molecular adrenal imaging with MTO PET in the management of (i) adrenal incidentalomas which are deemed indeterminate on conventional anatomical imaging, and (ii) in patients with PA. However, an important limitation of MTO is the requirement for an on-site cyclotron due to the short half-life (t½=20mins) of Carbon-11, which potentially limits the application of this imaging modality to a relatively small number of NHS sites across the UK. Therefore, this thesis also describes first-in-human studies with a related novel radiotracer [18F]CETO, which has a longer half-life (t½=110mins), to determine whether it has the potential to facilitate more widespread access to molecular adrenocortical imaging. The first chapter summarises the current knowledge base, including providing an overview of the current literature pertaining to adrenal adenomas and available imaging modalities, with a particular focus on molecular imaging modalities. Chapter two describes the methods that are common among the research studies presented in the subsequent chapters. Chapter three highlights the role of MTO PET in enhancing decision-making and improving outcomes for a proportion of cases where conventional imaging may fail to accurately characterise adrenal incidentalomas (AIs). This chapter highlights how MTO can be used to distinguish the origin of the indeterminate AI, and how a combination of imaging modalities [e.g., FDG PET, 123I-metaiodobenzylguanidine (123I-MIBG)] can be used to characterise (a) the origin of the lesion i.e., adrenocortical or non-adrenocortical, and (b) determine the malignant potential of the lesion. This will increase the accuracy in detection of the underlying adrenal pathology associated with the AI, and in turn better guide the diagnostic pathway and proposed management of AIs, along with determining the prospective scanning frequency. In certain instances, I demonstrate how a combination of two imaging modalities may avert the need for unnecessary adrenal biopsy, which is commonly associated with low yield and often non-diagnostic, and unnecessary surgical resection. I then focus specifically on PA, with chapter four outlining the ability of MTO PET/CT to accurately distinguish between unilateral and bilateral disease, using either MTO alone, or in combination with AVS findings, to guide surgical management in PA patients through a retrospective series. The findings of the study permitted the creation of a decision matrix, so that clinicians can adopt a more systematic approach in using MTO PET/CT to guiding the decision to proceed to surgery. The positive findings from the retrospective study described in chapter four required validation in a prospective study design, which is addressed in the subsequent chapter. Chapter five describes a prospective multicentre study, MATCH, which evaluates the role of MTO PET/CT for lateralisation in PA by comparing findings with the current gold standard, AVS. Following on from both retrospective and prospective studies, a limitation that has been identified with reference to MTO is the short half-life, restricting synthesis to clinical sites with an on-site cyclotron which amounts to 18F]CETO, comprising of five healthy volunteers and six PA patients (three unilateral and three bilateral disease). We assess the safety, tolerability, and efficacy of the tracer, and adopt dexamethasone administration in the protocol to determine how this impacts on the signal-to-noise ratio. Additionally, dosimetry calculations were undertaken to determine how tracer uptake compares in different organs. Throughout the studies described, adrenal specimens were taken and analysed to confirm aldosterone-producing adenoma(s), and whether the type of lesion correlates with the pattern of tracer uptake of the radiotracer. However, only a small number of studies in the current literature have outlined how certain histopathological characteristics may also correlate with other factors in PA, including pre- and postoperative outcomes. I conclude with chapter 7, which describes how specific histopathological findings in PA may correlate with pre- and postoperative outcomes. I take advantage of our retrospective patient cohort, of which a significant proportion would have proceeded to MTO to determine the appropriateness of surgical intervention. Therefore, I was able to assess the relationship between histopathological features on resected adrenal specimens, and the pattern of MTO tracer uptake on PET imaging.The MATCH study was funded by the British Heart Foundation (BHF). The CETO study was funded by the MRC DPFS grant

Cotrimoxazole-Induced Hypoglycaemia in a Patient with Churg-Strauss Syndrome

Cotrimoxazole is a commonly used antimicrobial agent which is traditionally indicated in the management of pneumocystis infection of which HIV and immunosuppressed individuals are at high risk. Furthermore, it can be used on the long term for prophylactic indications. Hypoglycaemia following commencement of cotrimaoxazole is a rare adverse effect which was first described in 1988. We describe a case of hypoglycaemia shortly following initiation of cotrimoxazole indicated as long-term prophylaxis on a background of Churg-Strauss syndrome. The patient was symptomatic for hypoglycaemia despite simultaneous use of high-dose prednisolone; however, the hypoglycaemia did not require a hospital admission. We will explore the risk factors, monitoring requirements, and the mechanism by which co-trimoxazole induces hypoglycaemia

PET-guided repeat transsphenoidal surgery for previously deemed unresectable lateral disease in acromegaly.

OBJECTIVE: The object of this study was to determine if revision transsphenoidal surgery (TSS), guided by 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR), can lead to remission in patients with persistent acromegaly due to a postoperative lateral disease remnant. METHODS: The authors identified 9 patients with persistent acromegaly following primary intervention (TSS ± medical therapy ± radiotherapy) in whom further surgery had initially been discounted because of equivocal MRI findings with suspected lateral sellar and/or parasellar disease (cases with clear Knosp grade 4 disease were excluded). All patients underwent Met-PET/MRCR. Scan findings were used by the pituitary multidisciplinary team to inform decision-making regarding repeat surgery. Revision TSS was performed with wide lateral exploration as guided by the PET findings. Endocrine reassessment was performed at 6-10 weeks after surgery, with longitudinal follow-up thereafter. RESULTS: Met-PET/MRCR revealed focal tracer uptake in the lateral sellar and/or parasellar region(s) in all 9 patients, which correlated with sites of suspected residual tumor on volumetric MRI. At surgery, tumor was identified and resected in 5 patients, although histological analysis confirmed somatotroph tumor in only 4 cases. In the other 4 patients, no definite tumor was seen, but equivocal tissue was removed. Despite the uncertainty at surgery, all patients showed immediate significant improvements in clinical and biochemical parameters. In the 8 patients for whom long-term follow-up data were available, insulin-like growth factor 1 (IGF-1) was ≤ 1.2 times the upper limit of normal (ULN) in all subjects and ≤ 1 times the ULN in 6 subjects, and these findings have been maintained for up to 28 months (median 8 months, mean 13 months) with no requirement for adjunctive medical therapy or radiotherapy. No patient suffered any additional pituitary deficit or other complication of surgery. CONCLUSIONS: This study provides proof of concept that Met-PET/MRCR can be helpful in the evaluation of residual lateral sellar/parasellar disease in persistent acromegaly and facilitate targeted revision TSS in a subgroup of patients.This work was supported by the United Kingdom National Institute for Health Research Cambridge Biomedical Research Centre (W.A.B., R.S., O.K., D.G., H.C., J.M., I.M., M.G.) and by the Evelyn Trust, Cambridge