A Research Report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfillment of the requirements for the degree of Master of Medicine In the branch of Nuclear Medicine Johannesburg September 2013 / The use of Single Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI), with Technetium – 99m (Tc-99m) Sestamibi in conjunction with either exercise, pharmacologic stress or both is an established tool for both the diagnosis and prognostication of patients with ischemic heart disease. For perfusion imaging with SPECT, Tc-99m labeled radiopharmaceuticals (Sestamibi or Tetrofosmin) are commonly used. The major metabolic pathway for clearance of Sestamibi is the hepatobiliary system which creates difficulty in both visual and quantitative interpretation of myocardial perfusion, particularly of the inferior and infero-septal walls after reconstruction. Diluted lemon juice, an acid-rich drink is an alimentary cholekinetic that facilitates Sestamibi transit through the liver. Whole milk stimulates liver clearance as well as increases peristaltic movement. The aim of the study was to determine which protocol would be the best to reduce interfering infra-cardiac activity and therefore result in an improvement in image quality. We had three groups, comparing the use of full fat milk, diluted lemon juice and a control group that had no intervention. All patients referred to our institution for MPI from November 2009 to May 2012 were enrolled in the study. A total of six hundred and thirty (630) patients who fulfilled the inclusion criteria were randomized without stratification into three groups. Group 0 (G0) were given diluted lemon juice, 246 patients; full fat milk to group 1 (G1), 313 patients and group 2 (G2); 71 patients, had no intervention. The latter was the control group. Raw data of both the stress and rest images were visually and quantitatively assessed by two Nuclear Medicine physicians for the presence of infra-cardiac activity. The physicians were blinded to the intervention received and the data were reviewed simultaneously. The administration of milk or lemon juice resulted in a significant decrease in the intensity of infra-cardiac activity compared to the control group. This improvement was even more significant in the milk group for patients done during rest myocardial perfusion imaging.

No description available.

The diagnosis and treatment of cerebrovascular disease, such as stroke and vascular lesions in the brain, requires knowledge of the status of brain tissue and cerebral arteries. Perfusion imaging and angiography offer information on blood flow to the tissue and through the brain-feeding arteries. A variety of imaging modalities exist to assess brain haemodynamics, including measures of cerebral blood flow and other parameters, however many of these are invasive and/or involve the use of contrast agents toxic to certain patient populations. One non-invasive magnetic resonance imaging alternative for perfusion imaging and angiography, which also provides vessel specific blood flow information, is vessel-encoded pseudocontinuous arterial spin labelling (VEPCASL). VEPCASL uses the blood as an endogenous tracer and can magnetically label the blood from different arteries of interest. The combination of VEPCASL with different imaging strategies can provide a map of the vascular perfusion territories in the brain, or dynamic information on blood flow through the cerebral arteries. The work in this thesis seeks to optimise and develop the encoding process of VEPCASL and accompanying angiographic readouts. Firstly, a rapid and automated method for calculating a minimal number of signal-to-noise ratio (SNR) efficient encodings, for any number and arrangement of vessels, was developed. Its use resulted in improved SNR in perfusion territories fed by more complicated vessel arrangements in the labelling plane. The labelling efficiency of VEPCASL, and its non-vessel-selective equivalent, PCASL, is affected by the presence of magnetic field inhomogeneities in the labelling plane. Consequently, a correction for phase offsets was introduced into the calculation of the optimised encodings. These encodings enabled the recovery of SNR in perfusion territories for PCASL and VEPCASL when phase offsets were present at the labelled arteries. As current VEPCASL angiography methods are relatively slow to acquire, an accelerated readout was developed to acquire two-dimensional vessel-selective dynamic angiograms in approximately one minute. A radial k-space trajectory was found to offer the best vessel definition and SNR. Three-dimensional (3D) angiograms provide the most detailed view of the cerebral vasculature for use in diagnosis and treatment of cerebrovascular disease. A 3D radial readout was optimised to acquire vessel-selective dynamic angiograms. These angiograms offer information on the structure of the vascular tree and how it is fed by the major arteries in the neck. The techniques developed here aim to increase the clinical viability and applicability of VEPCASL perfusion imaging and angiography. It is hoped that the techniques herein could be used in patient populations to add to and improve the diagnostic information available.

Tumors have several important hallmarks; anomalous and heterogeneous behaviors of their vascular structures, and high angiogenesis and neovascularization. Tumor tissue presents high blood flow (F) and extraction ratio (E) of contrast molecules. Consequently there is growing interest in non invasive methods for characterizing changes in tumor vasculature. Toft's model has been extensively used in the past in order to calculate Ktrans maps which take into consideration both F and E. However, in this thesis we argue that for accurate tumor characterization we need a model able to compute both F and E in tissue plasma. This project has been developed as part of a larger project, working toward building a Clinical Decision Support System (CDSS): an interactive expert computer software, that helps doctors and other health professionals make decisions regarding patient treatment progress. Using the Gamma Capillary Transit Time (GCTT) pharmacokinetic model we calculate F and E separately in a more realistic framework; unlike other models it takes into account the heterogeneity of the tumor, which depends on parameter a-1. a-1 is the width of the distribution of the capillary transit times within a tissue voxel. In more detail, a-1 expresses the heterogeneity of tissue microcirculation and microvasculature. We studied 9 patients pathologically diagnosed with glioblastoma multiforme (GBM), a common malignant type of brain tumor. Several physiological parameters including the blood flow and extraction ratio distributions were calculated for each patient. Then we investigated if these parameters can characterize early the patients' responsiveness to current treatment; we assessed the classification potential based on the actual therapy outcome. To this end, we present a novel analysis framework which exploits the new parameter a-1 and organizes each voxel into four sub-region. Our results indicate that early characterization of response based on GCCT can be significantly improved by focusing on tumor voxels from a specific sub-region.

A research report submitted to the Faculty of Health Sciences in fulfilment of the requirements for the degree of Master of Medicine, in Internal Medicine at the University of Witwatersrand, Johannesburg. September 2017 / Differentiating ischaemic left ventricular dysfunction (ILVD) from non-ischaemic left ventricular dysfunction (NILVD) is crucial since appropriately selected patients may benefit from coronary revascularisation. The aim of this study was to evaluate the diagnostic utility of myocardial perfusion imaging (MPI) in patients presenting with left ventricular dysfunction using coronary angiography (CA) as the gold standard. Methods This single centre retrospective study was conducted in 52 patients with heart failure with a reduced ejection fraction (EF< 40%) who had both MPI as well as CA at CHBAH between January 2005 and December 2012. ILVD was diagnosed when the distribution and severity of coronary disease on CA was sufficient to account for the degree of left ventricular dysfunction. Results From a total of 52 patients, 33 (63%) had ILVD and 19 (37%) had NILVD. As compared to patients with NILVD, those with ILVD were more likely to be Indian and White (p=0.0014), have more coronary risk factors (5(2) vs 3(2), p < 0.0001) and more commonly have q waves on the ECG (0% vs 55%, p < 0.0001). MPI had a sensitivity of 100% (95% CI 66-100%) and specificity of 52.63% (95% CI 30.18 - 75.08) for the diagnosis of ILVD. The presence of fixed perfusion defects on MPI was the best predictor of ILVD. Conclusion MPI has high sensitivity but low specificity for the diagnosis of ILVD. This makes it a useful screening test for the exclusion of coronary artery disease in patients presenting with heart failure. / MT2018

abstract: In medical imaging, a wide variety of methods are used to interrogate structural and physiological differences between soft tissues. One of the most ubiquitous methods in clinical practice is Magnetic Resonance Imaging (MRI), which has the advantage of limited invasiveness, soft tissue discrimination, and adequate volumetric resolution. A myriad of advanced MRI methods exists to investigate the microstructural, physiologic and metabolic characteristics of tissue. For example, Dynamic Contrast Enhanced (DCE) and Dynamic Susceptibility Contrast (DSC) MRI non-invasively interrogates the dynamic passage of an exogenously administered MRI contrast agent through tissue to quantify local tracer kinetic properties like blood flow, vascular permeability and tissue compartmental volume fractions. Recently, an improved understanding of the biophysical basis of DSC-MRI signals in brain tumors revealed a new approach to derive multiple quantitative biomarkers that identify intrinsic sub-voxel cellular and vascular microstructure that can be used differentiate tumor sub-types. One of these characteristic biomarkers called Transverse Relaxivity at Tracer Equilibrium (TRATE), utilizes a combination of DCE and DSC techniques to compute a steady-state metric which is particularly sensitive to cell size, density, and packing properties. This work seeks to investigate the sensitivity and potential utility of TRATE in a range of disease states including Glioblastomas, Amyotrophic Lateral Sclerosis (ALS), and Duchenne’s Muscular Dystrophy (DMD). The MRC measures of TRATE showed the most promise in mouse models of ALS where TRATE values decreased with disease progression, a finding that correlated with reductions in myofiber size and area, as quantified by immunohistochemistry. In the animal models of cancer and DMD, TRATE results were more inconclusive, due to marked heterogeneity across animals and treatment state. Overall, TRATE seems to be a promising new biomarker but still needs further methodological refinement due to its sensitivity to contrast to noise and further characterization owing to its non-specificity with respect to multiple cellular features (e.g. size, density, heterogeneity) that complicate interpretation. / Dissertation/Thesis / Masters Thesis Biomedical Engineering 2018

A angiografia coronariana por tomografia computadorizada (ACTC) é um exame bem estabelecido no diagnóstico da doença arterial coronariana. Entretanto, segmentos coronarianos submetidos a implante de stent podem apresentar limitação na avaliação luminal. O objetivo deste estudo é avaliar o valor adicional da perfusão miocárdica por tomografia computadorizada (PMTC) à avaliação anatômica isolada pela ACTC em portadores de stent, tendo o cateterismo (CATE) como referência. Quarenta e seis pacientes (56,9±7,2 anos, 28 homens) com indicação clínica de CATE em até 60 dias foram submetidos à avaliação combinada de ACTC e PMTC, por meio de tomógrafo de 64 detectores (Aquillion 64, Toshiba). A aquisição foi iniciada com a fase de estresse (PMTC) usando-se dipiridamol a 0,56mg/kg/4min e 60ml de contraste a 3ml/s, seguido de reversão com aminofilina 240mg e metoprolol (até 20mg). Em seguida, realizou-se a ACTC com 80-90ml de constraste a 5ml/s. Os dados da PMTC, da ACTC, e do CATE foram analisados por dois observadores independentes, sem informações clínicas dos pacientes. Primariamente analisou-se a ACTC, seguida da avaliação da PMTC. Concluída esta fase, os observadores tinham a possibilidade de reclassificar os segmentos coronarianos submetidos a stent cuja avaliação estivesse limitada ou inadequada por artefatos. A dose total média de radiação foi 15,83±4,93 mSv e todos os exames foram adequados. Um total de 129 segmentos coronarianos foi avaliado na ACTC, bem como os respectivos territórios miocárdicos pela PMTC. Destes, 54 territórios (42%) eram relacionados à presença de stents, sendo 19 com stents de avaliação adequada e 23 com avaliação luminal limitada, porém possível, e 12 segmentos de avaliação inadequada (sem possibilidade de avaliação luminal). Os valores de sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia para a ACTC isolada nos territórios com stents foram de, respectivamente: 85%, 76%, 85%, 76% e 81%, e com o uso combinado da ACTC + PMTC foram de, respectivamente 88%, 95%, 97%, 83% e 92% (p=0,0314). Nos territórios com stent e avaliação luminal prejudicada (limitada ou inadequada) os valores para análise da ACTC isolada foram de, respectivamente: 83%, 71%, 75%, 80% e 77% e após a análise da ACTC + PMTC foram de, respectivamente: 89%, 94%, 94%, 89% e 92% (p = 0,0441). A avaliação combinada da ACTC + PMTC permitiu melhorar a acurácia diagnóstica da avaliação de obstrução coronariana significativa em pacientes portadores de stents, comparativamente à avaliação isolada da ACTC / Coronary computed tomography angiography (coronary CTA) is a well established examination in the diagnosis of coronary artery disease (CAD). However, the segments with prior coronary stent implantation may have limited luminal evaluation. The aim of this study is to assess the incremental value of myocardial computed tomography perfusion (myocardial CTP) to the anatomical assessment by coronary CTA alone in patients with stents, using catheterization (CAT) as a reference method. Forty-six patients (56.9 ± 7.2 years, 28 men) referred to CAT by clinical indication within 60 days, were evaluated with combined evaluation of coronary CTA and myocardial CTP through 64-detector CT scanner (Aquillion 64, Toshiba). The acquisition protocol began with the stress phase (myocardial CTP), using dipyridamole to 0.56 mg/kg/4min and 60ml of contrast (3ml/s), followed by a bolus of aminophylline 240 mg and metoprolol (up to 20mg). After, it was performed the coronary CTA wih 80-90ml of contrast (5 ml/s). Data from the myocardial CTP, coronary CTA and CAT were analyzed by two independent observers, with no knowledge to clinical information. The observers reviewed the coronary CTA findings, and in a second time performed the evaluation of myocardial CTP. So, they had the possibility to reclassify segments with coronary stent that were considered with limited or inadequate assessment due to artifacts. Mean total dose of radiation was 15.83 ± 4.93 mSv, and all examinations were interpretable. A total of 129 coronary segments were evaluated by coronary CTA, and also were their correspondent myocardial territories by myocardial CTP. Of these, 54 territories (42%) were related to the presence of stents, 19 stents with adequate evaluation, 23 with limited evaluation, but possible, and 12 with inadequate evaluation (no luminal assessment possible). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the coronary CTA in territories with stents were respectively: 85%, 76%, 85%, 76% and 81%, and the combined use of coronary CTA + Myocardial CTP were respectively 88%, 95%, 97%, 83% and 92% (p=0.0314). In territories with impaired luminal stent evaluation (limited or inadequate), the values for analysis of coronary CTA alone were: 83%, 71%, 75%, 80% and 77%, and after analysis of myocardial CTP were, respectively: 89%, 94%, 94%, 89% and 92% (p = 0.0441). The combined evaluation of the coronary CTA and myocardial CTP has improved the diagnostic accuracy of the evaluation of significant coronary obstruction in patients with stents, compared to the assessment of coronary CTA alone

Heidelberg, Univ., Diss., 2005.

Stroke is a major cause of disability and death worldwide. Although different clinical studies and trials used Magnetic Resonance Imaging (MRI) to examine patterns of change in different imaging modalities (eg: perfusion and diffusion), we still lack a clear and definite answer to the question: “How does an acute ischemic stroke lesion grow?” The inability to distinguish viable and dead tissue in abnormal MR regions in stroke patients weakens the evidence accumulated to answer this question, and relying on static snapshots of patient scans to fill in the spatio-temporal gaps by “thinking/guessing” make it even harder to tackle. Different opposing observations undermine our understanding of ischemic stroke evolution, especially at the acute stage: viable tissue transiting into dead tissue may be clear and intuitive, however, “visibly” dead tissue restoring to full recovery is still unclear. In this thesis, we search for potential answers to these raised questions from a novel dynamic modelling perspective that would fill in some of the missing gaps in the mechanisms of stroke evolution. We divided our thesis into five parts. In the first part, we give a clinical and imaging background on stroke and state the objectives of this thesis. In the second part, we summarize and review the literature in stroke and medical imaging. We specifically spot gaps in the literature mainly related to medical image analysis methods applied to acute-subacute ischemic stroke. We emphasize studies that progressed the field and point out what major problems remain. Noticeably, we have discovered that macroscopic (imaging-based) dynamic models that simulate how stroke lesion evolves in space and time were completely overlooked: an untapped potential that may alter and hone our understanding of stroke evolution. Progress in the dynamic simulation of stroke was absent –if not inexistent. In the third part, we answer this new call and apply a novel current-based dynamic model âpreviously applied to compare the evolution of facial characteristics between Chimpanzees and Bonobos [Durrleman 2010] – to ischemic stroke. This sets a robust numerical framework and provides us with mathematical tools to fill in the missing gaps between MR acquisition time points and estimate a four-dimensional evolution scenario of perfusion and diffusion lesion surfaces. We then detect two characteristics of patterns of abnormal tissue boundary change: spatial, describing the direction of change –outward as tissue boundary expands or inward as it contracts–; and kinetic, describing the intensity (norm) of the speed of contracting and expanding ischemic regions. Then, we compare intra- and inter-patients estimated patterns of change in diffusion and perfusion data. Nevertheless, topology change limits this approach: it cannot handle shapes with different parts that vary in number over time (eg: fragmented stroke lesions, especially in diffusion scans, which are common). In the fourth part, we suggest a new mathematical dynamic model to increase rigor in the imaging-based dynamic modeling field as a whole by overcoming the topology-change hurdle. Metamorphosis. It morphs one source image into a target one [Trouvé 2005]. In this manuscript, we extend it into dealing with more than two time-indexed images. We propose a novel extension of image-to-image metamorphosis into longitudinal metamorphosis for estimating an evolution scenario of both scattered and solitary ischemic lesions visible on serial MR. It is worth noting that the spatio-temporal metamorphosis we developed is a generic model that can be used to examine intensity and shape changes in time-series imaging and study different brain diseases or disorders. In the fifth part, we discuss our main findings and investigate future directions to explore to sharpen our understanding of ischemia evolution patterns.

A angiografia coronariana por tomografia computadorizada (ACTC) é um exame bem estabelecido no diagnóstico da doença arterial coronariana. Entretanto, segmentos coronarianos submetidos a implante de stent podem apresentar limitação na avaliação luminal. O objetivo deste estudo é avaliar o valor adicional da perfusão miocárdica por tomografia computadorizada (PMTC) à avaliação anatômica isolada pela ACTC em portadores de stent, tendo o cateterismo (CATE) como referência. Quarenta e seis pacientes (56,9±7,2 anos, 28 homens) com indicação clínica de CATE em até 60 dias foram submetidos à avaliação combinada de ACTC e PMTC, por meio de tomógrafo de 64 detectores (Aquillion 64, Toshiba). A aquisição foi iniciada com a fase de estresse (PMTC) usando-se dipiridamol a 0,56mg/kg/4min e 60ml de contraste a 3ml/s, seguido de reversão com aminofilina 240mg e metoprolol (até 20mg). Em seguida, realizou-se a ACTC com 80-90ml de constraste a 5ml/s. Os dados da PMTC, da ACTC, e do CATE foram analisados por dois observadores independentes, sem informações clínicas dos pacientes. Primariamente analisou-se a ACTC, seguida da avaliação da PMTC. Concluída esta fase, os observadores tinham a possibilidade de reclassificar os segmentos coronarianos submetidos a stent cuja avaliação estivesse limitada ou inadequada por artefatos. A dose total média de radiação foi 15,83±4,93 mSv e todos os exames foram adequados. Um total de 129 segmentos coronarianos foi avaliado na ACTC, bem como os respectivos territórios miocárdicos pela PMTC. Destes, 54 territórios (42%) eram relacionados à presença de stents, sendo 19 com stents de avaliação adequada e 23 com avaliação luminal limitada, porém possível, e 12 segmentos de avaliação inadequada (sem possibilidade de avaliação luminal). Os valores de sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo e acurácia para a ACTC isolada nos territórios com stents foram de, respectivamente: 85%, 76%, 85%, 76% e 81%, e com o uso combinado da ACTC + PMTC foram de, respectivamente 88%, 95%, 97%, 83% e 92% (p=0,0314). Nos territórios com stent e avaliação luminal prejudicada (limitada ou inadequada) os valores para análise da ACTC isolada foram de, respectivamente: 83%, 71%, 75%, 80% e 77% e após a análise da ACTC + PMTC foram de, respectivamente: 89%, 94%, 94%, 89% e 92% (p = 0,0441). A avaliação combinada da ACTC + PMTC permitiu melhorar a acurácia diagnóstica da avaliação de obstrução coronariana significativa em pacientes portadores de stents, comparativamente à avaliação isolada da ACTC / Coronary computed tomography angiography (coronary CTA) is a well established examination in the diagnosis of coronary artery disease (CAD). However, the segments with prior coronary stent implantation may have limited luminal evaluation. The aim of this study is to assess the incremental value of myocardial computed tomography perfusion (myocardial CTP) to the anatomical assessment by coronary CTA alone in patients with stents, using catheterization (CAT) as a reference method. Forty-six patients (56.9 ± 7.2 years, 28 men) referred to CAT by clinical indication within 60 days, were evaluated with combined evaluation of coronary CTA and myocardial CTP through 64-detector CT scanner (Aquillion 64, Toshiba). The acquisition protocol began with the stress phase (myocardial CTP), using dipyridamole to 0.56 mg/kg/4min and 60ml of contrast (3ml/s), followed by a bolus of aminophylline 240 mg and metoprolol (up to 20mg). After, it was performed the coronary CTA wih 80-90ml of contrast (5 ml/s). Data from the myocardial CTP, coronary CTA and CAT were analyzed by two independent observers, with no knowledge to clinical information. The observers reviewed the coronary CTA findings, and in a second time performed the evaluation of myocardial CTP. So, they had the possibility to reclassify segments with coronary stent that were considered with limited or inadequate assessment due to artifacts. Mean total dose of radiation was 15.83 ± 4.93 mSv, and all examinations were interpretable. A total of 129 coronary segments were evaluated by coronary CTA, and also were their correspondent myocardial territories by myocardial CTP. Of these, 54 territories (42%) were related to the presence of stents, 19 stents with adequate evaluation, 23 with limited evaluation, but possible, and 12 with inadequate evaluation (no luminal assessment possible). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the coronary CTA in territories with stents were respectively: 85%, 76%, 85%, 76% and 81%, and the combined use of coronary CTA + Myocardial CTP were respectively 88%, 95%, 97%, 83% and 92% (p=0.0314). In territories with impaired luminal stent evaluation (limited or inadequate), the values for analysis of coronary CTA alone were: 83%, 71%, 75%, 80% and 77%, and after analysis of myocardial CTP were, respectively: 89%, 94%, 94%, 89% and 92% (p = 0.0441). The combined evaluation of the coronary CTA and myocardial CTP has improved the diagnostic accuracy of the evaluation of significant coronary obstruction in patients with stents, compared to the assessment of coronary CTA alone