Automated quantification of stroke damage on brain computed tomography scans: e-ASPECTS

Emergency radiological diagnosis of acute ischaemic stroke requires the accurate detection and appropriate interpretation of relevant imaging findings. Non-contrast computed tomography (CT) provides fast and low-cost assessment of the early signs of ischaemia and is the most widely used diagnostic modality for acute stroke. The Alberta Stroke Program Early CT Score (ASPECTS) is a quantitative and clinically validated method to measure the extent of ischaemic signs on brain CT scans. The CE-marked electronic-ASPECTS (e-ASPECTS) software automates the ASPECTS score. Anglia Ruskin Clinical Trials Unit (ARCTU) independently carried out a clinical investigation of the e-ASPECTS software, an automated scoring system which can be integrated into the diagnostic pathway of an acute ischaemic stroke patient, thereby assisting the physician with expert interpretation of the brain CT scan. Here we describe a literature review of the clinical importance of reliable assessment of early ischaemic signs on plain CT scans, and of technologies automating these processed scoring systems in ischaemic stroke on CT scans focusing on the e-ASPECTS software. To be suitable for critical appraisal in this evaluation, the published studies needed a sample size of a minimum of 10 cases. All randomised studies were screened and data deemed relevant to demonstration of performance of ASPECTS were appraised. The literature review focused on three domains: i) interpretation of brain CT scans of stroke patients, ii) the application of the ASPECTS score in ischaemic stroke, and iii) automation of brain CT analysis. Finally, the appraised references are discussed in the context of the clinical impact of e-ASPECTS and the expected performance, which will be independently evaluated by a non-inferiority study conducted by the ARCTU

Development of a novel MRI technique for imaging the ischaemic penumbra in experimental stroke

In Scotland, stroke is the third most common cause of death behind heart disease and cancer. However, most strokes are not fatal and can cause severe disability, with one third of survivors still functionally dependent after one year. The advent of recombinant tissue plasminogen activator (rT-PA) as a thrombolytic modality revolutionised the treatment for ischaemic stroke, providing a treatment aimed to promptly restore nutritional blood flow to the ischaemic penumbra, a transient tissue state which is amenable to salvage. Crucially, patient ineligibility from a multitude of factors (including the narrow time window for benefit and the risk of intracranial haemorrhage) means that fewer than 10% of all stroke patients are thrombolysed. Positive identification of penumbra is not employed in the current intravenous rT-PA administration strategy, which is instead based on two main prerequisites: stroke patients in whom intracerebral haemorrhage has been excluded with non-contrast computed tomography (CT) and who also present within 4.5 hours of symptom onset. The technical impracticalities and limited availability of the gold standard penumbral imaging modality, multitracer 15O positron emission tomography (PET), and the lack of standardised thresholds to identify penumbra using non-contrast CT have hindered the development and inclusion of routine brain imaging in the management of acute stroke patients. An alternative research tool which may potentially be used in clinical practice is magnetic resonance imaging (MRI) which defines penumbra on the basis of diffusion-perfusion (DWI/PWI) mismatch. However, this provides an imprecise measure of penumbra and fails to identify tissue viability. Current PET-derived definitions of penumbra use metabolic indices such as oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), which are not fully incorporated into MR definitions. This thesis presents an alternative MRI method for identifying the metabolic penumbra in a rodent model of focal cerebral ischaemia. This utilises an MRI sequence similar to that used in functional MRI (fMRI) techniques, and uses 100% oxygen inhalation as a biotracer to detect penumbral tissue. Specifically, by using a blood oxygen level dependent (BOLD) T2*-weighted sequence in which changes in the deoxyhaemoglobin:oxyhaemoglobin ratio are detected - in conjunction with a transient hyperoxic challenge (Oxygen Challenge (OC) paradigm: 5 minutes breathing air followed by 5 minutes breathing 100% oxygen) - penumbral tissue can be distinguished from adjacent ischaemic core and benign oligaemia (Santosh et al, 2008). Changes in CBF, cerebral blood volume (CBV), tissue oxygenation, and oxidative metabolism can all influence the T2* signal (Ramsay et al, 1993; Corfield et al, 2001), so it was important to evaluate the possibility that factors other than tissue metabolism were influencing the signal change during OC. An initial study was performed which showed that baseline CBF did not influence T2* signal response to OC, whilst a greater increase in the percentage change in arterial oxygen saturation following OC caused an increased magnitude in T2* percentage signal change in contralateral tissue and penumbra, but not in ischaemic core. Arterial oxygen levels (PaO2) affect the magnitude of the T2* signal change to OC, with lower baseline PaO2 levels amplifying the T2* signal response in metabolically active regions, implying that careful control of physiological variables may optimise the T2*OC technique. The first validation study used [14C] 2-deoxyglucose autoradiography to determine the metabolic status of penumbra defined by T2*OC MRI. The results confirmed that glucose metabolism in the T2*OC-defined penumbra was comparable to contralateral values, whereas markedly different levels of glucose metabolism were evident in the ADC-derived ischaemic core and an adjacent region of increased 2DG phosphorylation. From this, it was concluded that metabolic information could be yielded from the ischaemic brain that may improve delineation of the penumbra using the OC technique. As penumbral tissue must fulfil the fundamental criteria of being potentially salvageable and responsive to therapy, the consequences of reperfusion on the T2*OC-defined penumbra was tested. This study confirmed that T2*OC-defined penumbra displayed a T2* signal change significantly higher than contralateral tissue during ischaemia which subsequently returned to contralateral levels following reperfusion and did not progress to infarction when assessed at day 7 following stroke. Finally, the spatiotemporal characteristics of the T2*OC-defined penumbra were investigated and compared with DWI/PWI mismatch-defined penumbra. Serial scanning demonstrated that T2*OC penumbra behaved in a similar manner to tissue defined by traditional mismatch criterion. The spatial location and tissue volumes of penumbra were similar with both methods, showing that, in animals where mismatch tissue volume reduced over time, T2*OC penumbra reduced similarly, and in animals where mismatch volume remained static over time, T2*OC-defined penumbra behaved similarly. Additionally, an interesting finding arose in the latter study which showed that ischaemic damage continues to progress beyond 4 hours following permanent MCAO, which may be relevant to the calculation of ADC and CBF thresholds used in defining DWI/PWI mismatch. Collectively, the preclinical data support the potential of T2*OC to discriminate tissue compartments in acute stroke based on metabolic status which thereby provides an alternative and improved means of defining the ischaemic penumbra

Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion:Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal

AbstractOver the last 15years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: “how does an ischemic stroke evolve?” Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi-automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model applied to ischemic stroke, we have insights into relevant microscopic dynamic models simulating the evolution of brain ischemia in the hope to further promising and challenging 4D imaging-based dynamic models. By depicting the major pitfalls and the advanced aspects of the different reviewed methods, we present an overall critique of their performances and concluded our discussion by suggesting some recommendations for future research work focusing on one or more of the three addressed problems

Outcomes after acute intracerebral haemorrhage

Primary Intracerebral haemorrhage is a severe form of stroke with poor prognosis attributed to haematoma characteristics. High blood pressure is present during the acute phase of intracerebral haemorrhage and associated with poor outcome in part through expansion of haematoma. Data from the ‘Efficacy of Nitric Oxide in Stroke trial’ (ENOS) was used to analyse the performance characteristics of qualitative and quantitative descriptors of intracerebral haematoma. The results showed that formal measurement of haemorrhage characteristics and visual estimates are reproducible. Intracerebral haemorrhage volumes measured using the modified ABC/2 formula were significantly lower compared to standard ABC/2 and computer assisted semi-automatic segmentation. In 629 patients with intracerebral haemorrhage presenting within 48 hours, the effect of blood pressure lowering with transdermal glyceryl trinitrate was assessed. Glyceryl trinitrate lowered blood pressure, was safe but did not improve functional outcome. In a small group of patients treated within 6 hours, glyceryl trinitrate improved functional outcome. Analysis of 246 patients with acute intracerebral haemorrhage from ENOS was undertaken to assess whether there were any differences in functional outcome among those who continued prior antihypertensive drugs during the immediate stroke period compared to those assigned to stop temporarily for 7 days. The results were neutral indicating that there was no benefit in those who continued treatment. Data of 1,011 patients with intracerebral haemorrhage in hyperacute trials from the VISTA collaboration showed differences in baseline characteristics and functional outcomes among patients from various ethnic backgrounds. A systematic review was updated to assess the effect of 26 randomised controlled trials that aimed to alter blood pressure within one week of acute stroke. The results showed that blood pressure reduction did not improve functional outcome irrespective of stroke type. When examined by time, treatment within 6 hours appeared to benefit but the number of patients were small and more studies are needed. The analysis also showed that continuing prestroke antihypertensive drugs in the immediate period after stroke did not benefit and might be harmful. In summary, this thesis provides new information on parameters used to estimate intracerebral haematoma, relationship between management of blood pressure and outcomes after haemorrhagic stroke. The work supports testing of whether very early blood pressure lowering after ictus is beneficial as is being undertaken in ongoing randomised controlled trials. Adjusting for ethnic differences may further identify patients in whom treatment may confer measurable advantage

Thrombolysis in Acute Myocardial Infarction: An Electrocardiographic Study

The value of thrombolytic therapy in the treatment of acute myocardial infarction is now unchallenged following the publication of large scale clinical trials showing an impressive reduction in mortality. Intravenous administration of a thrombolytic agent in the early hours of myocardial infarction is established practice in all hospitals, from district generals to specialized cardiac centres. The aim is to obtain a patent artery, improve left ventricular function and decrease mortality. The effectiveness of intravenous therapy obviates the need for acute angiography and intracoronary administration, but a definitive statement concerning whether reperfusion has occurred cannot be made. The 12 lead ECG undergoes well recognised dynamic changes in the early phase of myocardial infarction. Successful lysis, either induced or spontaneous, will modify these changes. Whether these modifications can be quantified and used as simple non invasive tests of reperfusion, myocardial salvage and infarct size has caused much speculation. To have such a simple, widely available, reproducible and inexpensive tool would be highly desirable in a clinical setting. This thesis has addressed these questions. The first study demonstrated the rapid fall in ST segment elevation occurring in response to thrombolysis, and introduced a measurement which expresses this fall as a proportion of the admission value. This is termed the Fractional Change and can be applied to either 24 hour tape recordings or to the 12 lead ECG. A Fractional Change Value > 0.5 occurring by 2-3 hours following therapy is highly specific and sensitive for reperfusion. The next study examined whether an electrocardiographic marker of infarct size, the QRS score, was attenuated in patients achieving successful reperfusion compared with a historical cohort of patients with infarctions given no therapy other than simple analgesia. Only patients with anterior infarcts were studied, and although both groups had similar areas of myocardium at jeopardy on admission, the group of patients achieving successful reperfusion had a significant reduction in the QRS score at 48 hours compared to the control group. These initial studies showed that dynamic changes in the ECG can reflect both reperfusion and myocardial salvage, but are limited in that they were performed in relatively small numbers, and the ECG measurements were made and tabulated manually. A method for digitizing 12 lead ECG's with subsequent computer storage of data for comparative analysis has been developed, and incorporates an automatic QRS scoring system. The developmental work involved in setting this system up and its subsequent validation with inter- and intra-observer variation studies is presented in Chapter 5. This system was then used to follow the sequential ECG changes in a prospective angiographically controlled, double blind randomised trial of 128 patients comparing anistreplase with streptokinase. The 90 minute patency rates for both drugs were found to be the same (anistreplase 55%, streptokinase 53%) . Coronary angiography performed at 90 minutes post therapy allowed a detailed correlation between ECG changes on admission and acute coronary anatomy. The findings of this particular study showed that the height of ST segment elevation does not bear any relation to the age of the infarct, that there is a high incidence of reciprocal change early in the course of infarction, and that this is not related to coexisting disease or remote ischaemia, but is likely to be an electrocardiographic mirror phenomenon. Examining the resolution of ST segment elevation and depression showed that it was the rate of fall which discriminates patent from non patent arteries, and that using a Fractional Change Value of 0. 5 to detect reperfusion, calculated at 2 hours post treatment from a single lead showing maximal ST segment elevation, gave the best sensitivity (81%) and specificity (60%), when compared with a number of different parameters. In addition, it appears that the presence of collaterals supplying the infarct area could result in a high Fractional Change Value despite no antegrade perfusion. This study also confirmed that achievement of a patent artery early (i.e. before 90 minutes) significantly attenuated Q wave development, R wave loss and the QRS score in anterior infarction, but did not affect electrocardiographic markers of infarct size when applied to inferior infarcts. In summary, this thesis provides a detailed study of the electrocardiographic changes taking place in acute myocardial infarction, especially as a consequence of treating with thrombolysis, quantitates these changes and shows where they may be used in a clinical setting as non-invasive tests to aid patient management

Case series of breast fillers and how things may go wrong: radiology point of view

INTRODUCTION: Breast augmentation is a procedure opted by women to overcome sagging breast due to breastfeeding or aging as well as small breast size. Recent years have shown the emergence of a variety of injectable materials on market as breast fillers. These injectable breast fillers have swiftly gained popularity among women, considering the minimal invasiveness of the procedure, nullifying the need for terrifying surgery. Little do they know that the procedure may pose detrimental complications, while visualization of breast parenchyma infiltrated by these fillers is also deemed substandard; posing diagnostic challenges. We present a case series of three patients with prior history of hyaluronic acid and collagen breast injections. REPORT: The first patient is a 37-year-old lady who presented to casualty with worsening shortness of breath, non-productive cough, central chest pain; associated with fever and chills for 2-weeks duration. The second patient is a 34-year-old lady who complained of cough, fever and haemoptysis; associated with shortness of breath for 1-week duration. CT in these cases revealed non thrombotic wedge-shaped peripheral air-space densities. The third patient is a 37‐year‐old female with right breast pain, swelling and redness for 2- weeks duration. Previous collagen breast injection performed 1 year ago had impeded sonographic visualization of the breast parenchyma. MRI breasts showed multiple non- enhancing round and oval shaped lesions exhibiting fat intensity. CONCLUSION: Radiologists should be familiar with the potential risks and hazards as well as limitations of imaging posed by breast fillers such that MRI is required as problem-solving tool