Surrogate driven respiratory motion model derived from CBCT projection data

Cone Beam Computed Tomography (CBCT) is the most common imaging method for Image Guided Radiation Therapy (IGRT). However due to the slow rotating gantry, the image quality of CBCT can be adversely affected by respiratory motion, as it blurs the tumour and nearby organs at risk (OARs), which makes visualization of organ boundaries difficult, in particular for organs in the thoracic region. Currently one approach to tackle the problem of respiratory motion is the use of respiratory motion model to compensate for the motion during CBCT image reconstruction. The overall goal of this work is to estimate the 3D motion, including the breath-to-breath variability, on the day of treatment directly from the CBCT projection data, without requiring any external devices. The work presented here consist of two main parts: firstly, we introduce a novel data driven method based on Principal Component Analysis PCA, with the goal to extract a surrogate signal related to the internal anatomy from the CBCT projections. Secondly, using the extracted signals, we use surrogate-driven respiratory motion models to estimate the patient’s 3D respiratory motion. We utilized a recently developed generalized framework that unifies image registration and correspondence model fitting into a single optimization. This enables the model to be fitted directly to unsorted/unreconstructed data (CBCT projection data), thereby allowing an estimate of the patient’s respiratory motion on the day of treatment. To evaluate our methods, we have used an anthropomorphic software phantom combined with CBCT projection simulations. We have also tested the proposed method on clinical data with promising results obtained

Motion Compensation for Free-Breathing Abdominal Diffusion-Weighted Imaging (MoCo DWI)

Diffusion-weighted imaging (DWI) is a common technique in medical diagnostics. One challenge of thoracic and abdominal DWI is respiratory motion which can result in motion artifacts. To eliminate these artifacts, a new kind of retrospective, respiratory motion compensation for DWI was developed and tested. This new technique — MoCo DWI — is the first in DWI which provides fully-deformable motion compensation. To enable this, despite the low image quality of DWI, two free-breathing sequences were used: (1) a gradient echo sequence (GRE) with a configuration for optimal respiratory motion estimation and (2) a DWI in a configuration of clinical interest. The DWI acquisition was gated into 10 motion phases. Each motion phase was then co-aligned with the motion estimation. The implementation was tested with eleven volunteers. The results showed that MoCo DWI can reduce motion blurring in single b-value images, especially at the liver-lung interface. The improvement of ADC-maps was even more prominent. Individual slices showed motion induced artifacts which could be reduced or even eliminated by MoCo DWI. This was also reflected by expected more homogeneous ADC values in the liver in all data sets. These results promise to reduce measurements with limited diagnostic value while keeping or increasing patient comfort

Quantitative PET and SPECT

Since the introduction of personalized medicine, the primary focus of imaging has moved from detection and diagnosis to tissue characterization, the determination of prognosis, prediction of treatment efficacy, and measurement of treatment response. Precision (personalized) imaging heavily relies on the use of hybrid technologies and quantitative imaging biomarkers. The growing number of promising theragnostics require accurate quantification for pre- and post-treatment dosimetry. Furthermore, quantification is required in the pharmacokinetic analysis of new tracers and drugs and in the assessment of drug resistance. Positron Emission Tomography (PET) is, by nature, a quantitative imaging tool, relating the time–activity concentration in tissues and the basic functional parameters governing the biological processes being studied. Recent innovations in single photon emission computed tomography (SPECT) reconstruction techniques have allowed for SPECT to move from relative/semi-quantitative measures to absolute quantification. The strength of PET and SPECT is that they permit whole-body molecular imaging in a noninvasive way, evaluating multiple disease sites. Furthermore, serial scanning can be performed, allowing for the measurement of functional changes over time during therapeutic interventions. This Special Issue highlights the hot topics on quantitative PET and SPECT

In-house Implementation and Validation of the Mid-Position CT approach for the Treatment Planning of Respiration-induced Moving Tumours in Radiotherapy for Lung and Upper abdomen cancer

Tese mestrado integrado, Engenharia Biomédica e Biofísica (Engenharia Clínica e Instrumentação Médica) Universidade de Lisboa, Faculdade de Ciências, 2022A Radioterapia é uma das modalidades principais para tratamentos de foro oncológico que visa destruir a ação proliferativa das células cancerígenas e reduzir o volume tumoral. A sua ação terapêutica através do uso de radiação ionizante tem, subjacente, a máxima de irradiar o tumor com uma elevada dose, ao mesmo tempo que os órgãos de risco (OARs) adjacentes, são tanto quanto possível protegidos. Quando um tumor se localiza no pulmão ou abdómen superior, como no fígado ou pâncreas, o seu movimento devido à respiração pode alcançar até 4 cm, especialmente na direção crânio-caudal, aumentando as incertezas relativas à posição do tumor. No Centro Clínico Champalimaud (CCC), o planeamento convencional dos tratamentos de radioterapia faz uso de uma tomografia computadorizada (CT) que é adquirida aquando da respiração livre do doente e que, por isso, apresenta geralmente artefactos que podem ser uma fonte de erro durante o planeamento. Nos casos em que o movimento do tumor é considerável, é ainda adquirida uma tomografia computadorizada quadrimensional (4DCT) que consiste entre 8 e 10 CTs que representam fases do ciclo respiratório. Posteriormente, a 4DCT é utilizada para delinear o volume interno do alvo (ITV) que engloba toda a extensão do movimento do tumor. Apesar da estratégia do ITV garantir uma adequada cobertura do volume-alvo, os OARs ficam expostos a doses de radiação desnecessárias e a um maior risco de toxicidade. Este efeito é ainda mais preocupante em tratamentos hipofracionados, onde doses mais elevadas são administradas num número reduzido de frações. Nos últimos anos têm sido desenvolvidas estratégias que visam tornar os tratamentos de radioterapia mais eficazes. Uma delas é a reconstrução de uma CT que representa a posição média do doente ao longo do ciclo respiratório (Mid-P CT). Esta estratégia resulta em volumes de tratamento menores do que a estratégia do ITV, possibilitando o aumento da dose e maior controlo tumoral local. O primeiro passo para a reconstrução do Mid-P CT é o registo deformável de imagens (DIR) entre uma das fases da respiração (uma CT da 4DCT), definida como a fase de referência, e as restantes fases. Deste processo resultam campos vetoriais deformáveis (DVF) que contém informação do deslocamento dos tecidos. Os DVFs são subsequentemente utilizados para transformar cada uma das fases da respiração para a posição média. O método do Mid-P foi implementado com sucesso no Instituto do Cancro Holandês (NKI) em 2008. Apesar dos bons resultados clínicos, o número de centros de radioterapia que utiliza esta técnica é muito reduzido. Tal deve-se, por um lado, à inexistência de soluções comerciais com esta funcionalidade e, por outro, ao esforço necessário alocar para implementar e validar soluções desenvolvidas internamente. O presente projeto teve como principal objetivo implementar a estratégia do Mid-P no CCC (Portugal). Para tal, foi otimizado um módulo – RunMidP – desenvolvido para o software 3D Slicer, que calcula o Mid-P CT e estima a amplitude do movimento do tumor e OARs com base nos DVFs. Considerando que a precisão do módulo e a qualidade de imagem do Mid-P CT devem atender os requisitos para o planeamento em radioterapia, foram realizados testes para validar o módulo. Sempre que possível, a sua performance foi comparada com outras aplicações desenvolvidas para a implementação da técnica do Mid-P, nomeadamente com um protótipo desenvolvido pela empresa Mirada Medical Ltd. (Reino Unido) – Mirada – e com o software desenvolvido no NKI (Holanda) – Wimp. Os testes foram divididos em três estudos diferentes, cada um com um conjunto de dados diferente. No primeiro estudo (estudo A), foram utilizadas 4DCT de 2 fantomas digitais, cuja função respiratória e cardíaca foi modelada de forma simplificada, e de 18 doentes com tumores localizados no pulmão (N = 8), no fígado (N = 6) e no pâncreas (N = 4). Neste estudo, foram comparados dois algoritmos DIR disponíveis no software 3D Slicer, o Plastimatch e o Elastix, em termos da precisão do registo e da qualidade de imagem do Mid-P CT reconstruído. Foi ainda avaliado a capacidade dos softwares RunMidP e Mirada representarem corretamente a posição média do doente e as diferenças das amplitudes do movimento do tumor estimadas pelos dois softwares. No estudo B, foram realizados testes de verificação semelhantes aos supre mencionados, em imagens sintéticas provenientes de 16 doentes, desta vez com a vantagem de se conhecer o “verdadeiro” Mid-P CT e as “verdadeiras” amplitudes do movimento do tumor. Estes foram comparados com os resultados obtidos com os softwares RunMidP e Mirada. Ainda, as unidades de Hounsfield (HU) no Mid-P CT reconstruído por RunMidP e Mirada foram comparadas com as HU na fase de referência, de modo a verificar se os Mid P CTs produziriam diferenças dosimétricas relevantes. No último estudo (estudo C), a qualidade de imagem do Mid-P CT foi avaliada quantitativamente e qualitativamente. Durante a análise qualitativa, foi pedido a dois médicos especialistas que avaliassem a viabilidade dos Mid-P CTs, reconstruídos pelos três softwares (RunMidP, Mirada e Wimp), para o planeamento dos tratamentos. O tempo da reconstrução do Mid-P CT a partir da 4DCT foi de cerca de 1h. Ambos os algoritmos, Plastimach e Elastix, demonstraram ser adequados para DIR de imagens do pulmão e abdómen superior, com diferenças estatisticamente não significativas (p > 0.05) em termos da precisão do registo. Contudo, o Mid-P CT reconstruído com Elastix apresentou uma melhoria na qualidade de imagem, sendo assim o algoritmo DIR escolhido para ser implementado no RunMidP. Em termos de métricas aplicadas a contornos definidos manualmente, tais como a distância de Hausdorf (HD) e coeficiente de Dice (DSC), o erro do registo de imagem foi menor que 1 mm, dentro do contorno do tumor, e 2 mm no pulmão. Os Mid-P CTs reconstruídos com o RunMidP e Mirada apresentaram maiores diferenças, relativamente ao “verdadeiro” Mid-P CT, na região do diafragma e zonas de maior homogeneidade como, por exemplo, no ar presente no intestino. Contudo, para a maioria dos doentes do estudo B, o Mid-P CT reconstruído com o software Mirada apresentou maior índice de similaridade estrutural (SSIM) relativamente ao “verdadeiro” Mid-P CT. Estes resultados podem estar na origem do uso de diferentes algoritmos DIR, mas deveram-se principalmente a uma falha na aplicação das transformações deformáveis pelo módulo RunMiP que foi corrigida posteriormente. Ainda, as diferenças entre as amplitudes estimadas e previstas foram menores que 1 mm para 37 tumores (78,9%), que resultam em diferenças menores que 0.3mm quando convertidas em margens de planeamento. Para além disso, as diferenças nos valores de HU dos Mid-P CTs comparativamente à fase de referência foram, em média, de 1 HU no tumor e OARs. Foram também observadas melhorias na qualidade de imagem do Mid-P CT, nomeadamente um aumento da relação sinal-ruído (SNR) e diminuição dos artefactos. Estes resultados estão de acordo com a avaliação dos médicos que, em geral, consideraram que os Mid-P CTs reconstruídos pelos três softwares são adequados para o planeamento dos tratamentos. No entanto, os Mid-P CTs reconstruídos com dados 4DCT provenientes do CCC apresentaram classificações inferiores aos reconstruídos com dados 4DCT do NKI. Em suma, as modificações do algoritmo DIR Plastimach para Elastix e a correção do método para aplicar as transformações deformáveis, permitiram uma melhoria na qualidade de imagem do Mid P CT e melhor performance do algoritmo, respetivamente. O módulo RunMidP, neste projeto otimizado e validado, apresenta um forte potencial para a reconstrução e implementação da estratégia do Mid-P na clínica, com performance comparável a outras aplicações existentes (Mirada e Wimp). Atenção especial deve ser dada aos dados 4DCT de input que parecem afetar a qualidade de imagem final do Mid-P CT. No futuro, valerá a pena otimizar os parâmetros de aquisição e reconstrução da 4DCT de modo a melhorar a qualidade de imagem e, ainda, o módulo RunMidP pode potencialmente ser otimizado no que respeita ao tempo de reconstrução do Mid-P CT e à precisão do DIR.Radiotherapy for tumours in the thorax and upper abdomen is challenging since they move notably with breathing. To cover the whole extent of tumour motion, relatively large margins are added to treatment volumes, posing a higher risk of toxicity for surrounding organs-at-risk (OARs). The Mid Position (Mid-P) method accounts for breathing motion by using deformable image registration (DIR) to transform all phases of a 4DCT scan to a time-weighted average 3DCT scan (Mid-P CT). The Mid-P strategy results in smaller treatment volumes, potentially boosting the delivery of hypofractionated treatments. To bring the Mid-P approach to the Champalimaud Clinical Centre (CCC), an in-house Mid position software module – RunMidP – was optimized. The module reconstructs the Mid-P CT and estimates breathing motion amplitudes of tumours and relevant OARs. In addition, this project presents a set of experiments to evaluate the performance of the Mid-P method and its feasibility for clinical implementation. The experiments were conducted throughout three different studies using 4DCT data from 18 phantoms and 23 patients. In Study A, the accuracy and image quality of two DIR algorithms (Plastimatch and Elastix) were assessed using quantitative metrics applied on either warped images or manually delineated contours. The reproduction of the patient’s mean position by the Mid-P CT and the estimation of motion amplitudes were compared to a soon-to-be Mid-P commercial software developed by Mirada Medical Ltd. In Study B,similar experiments were performed, this time using a more rigorous reference – “true” Mid-P CT scans and “true” motion estimations. In Study C, the image quality of Mid P CT scans was assessed quantitatively and qualitatively. Both Plastimatch and Elastix registration showed comparable registration accuracy, although Elastix showed superior image quality of reconstructed Mid-P CTs. Based on contour metrics, the registration error was less than 2 mm. In-house Mid-P CTs showed a slightly lower match to ground truth Mid-P CTs than the ones reconstructed by the Mirada prototype due to differences in DIR methods and small shifts to the original image geometry. Higher image differences were found in the diaphragm lung interface, where the patient's anatomy moves faster due to breathing, and in homogeneous regions such as the air regions in the bowel. On the other hand, differences (estimated-predicted) in motion amplitudes smaller than 1 mm were observed in 37 moving tumours (78.7%), showing a good performance of the Mid-P algorithm. Regarding the image quality, improvements in the signal-to-noise ratio and removal of image artefacts in Mid-P CTs are great advantages for using them as the planning CT. Clinicians also gave a good assessment of the suitability of Mid-P CT scans for treatment planning. No significant differences were found in the performance of the RunMidP compared to other Mid-Position packages, although worse scores were given to the CCC dataset than the dataset from another hospital. The in-house Mid-position algorithm shows promising results regarding the use of the software module in radiotherapy for lung and upper abdomen cancer. Further exploration must be given to improve the registration accuracy, image quality of the input data, and speed up the reconstruction of the Mid-P CT scan

An investigation into the limitations of myocardial perfusion imaging

Myocardial Perfusion Imaging (MPI) plays a very important role in the management of patients with suspected Coronary Artery Disease and its use has grown despite the shortcomings of the technique. Significant progress has been made in identifying the causes of these shortcomings and many solutions been suggested in the literature but the clinical sensitivity and specificity of the technique is still well below optimum. Monte Carlo Simulation is a very useful tool in identifying and guiding the understanding of the existing problems in MPI and this present study utilised this method to establish the basis of the simulations to be used and the way to analyse the results so that many of the causes of the attenuation defects, when using MPI, could be identified. This was achieved by investigating the effect that the different anatomical parts of the thorax have on the attenuation defects caused. A further aspect investigated was the impact that self-absorption in the heart has on these defects. The variability of these defects were further investigated by altering the position and orientation of the heart itself within the thorax and determining the effect it has on the attenuation defects caused. Results indicate that the attenuation caused is a very complicated process, that the self-absorption of the heart plays an extremely important role and the impact of the different positions and orientation of the heart inside the thorax are also significant. The distortion caused on the images by these factors was demonstrated by the intensity losses in the basal part and an over-estimation in the apical parts, which were clearly observable on the final clinical images, with the potential to affect clinical interpretation. Attenuation correction procedures using transmission sources, have been available for some time, but have not been adopted widely, amidst concern that they introduce additional artefacts. This study determined the effectiveness of these methods by establishing the level of correction obtained and whether additional artefacts were introduced. This included the effectiveness of the compensation achieved with the use of the latest commercially available comprehensive correction techniques. The technique investigated was “Flash3D" from Siemens providing transmission based attenuation correction, depth-dependent resolution recovery and scatter correction. The comparison between the defects and intensity losses predicted by the Monte Carlo Simulations and the corrections provided by this commercial correction technique revealed that solution is compensating almost entirely for these problems and therefore do provide substantial progress in overcoming the limitations of MPI. As a result of the improvements gained from applying these commercially available techniques and the accuracy established in this study for the mentioned technique it is strongly recommended that these new techniques be embraced by the wider Nuclear Medicine community so that the limitations in MPI can be reduced in clinical environment. Non-withstanding the above gains made there remains room for improvement by overcoming the of use transmission attenuation correction techniques by replacing them with emission based techniques. In this study two new related emission based attenuation correction techniques have been suggested and investigated and provide a promising prospect of overcoming these limitations

Investigation of Personalised Post-Reconstruction Positron Range Correction in 68Ga Positron Emission Tomography Imaging

Positron range limits the spatial resolution of Positron Emission Tomography, reducing image quality and accuracy. This thesis investigated factors affecting the magnitude of positron range, developed a personalised approach to range correction, and demonstrated the approach using simulated, phantom and patient data. The Geant4 Application for Emission Tomography software was utilised to model positron range when emitted by radionuclides, namely 18F and 68Ga, in water, bone and lung. The impact of range blurring in lungs was found to be ten times larger than in bone and four times larger than in water or soft tissue, regardless of the positron energy. Range effects occurring with different isotopes (18F and 68Ga) were evaluated across measurement and reconstructed spatial resolutions. It was found that range correction was not necessary when using 18F for voxel sizes larger than 4 mm. In contrast, range correction was required for images generated using 68Ga, particularly within or adjacent to the lung. An iterative, post-reconstruction range correction method was developed which relied only on the measured data. The correction method was validated in both simulation and phantom studies. Image quality and quantification accuracy of corrected images was shown to be superior when imaging with 68Ga. Importantly, the range correction suppressed and controlled image noise at high iteration numbers. Finally, in a patient study, image noise in regions of uniform uptake was significantly increased by ~2% (p<0.05), yet mean standardised uptake values remained unchanged after correction, showing the same uptake for normal radionuclide distributions. The lesion contrast and maximum uptake values were improved by 20% and 45%, respectively with statistical significance (p<0.05). Although these promising results show that the proposed method of range correction can be generalised to reconstructed images regardless of measurement system, acquisition parameters and radionuclides used, further research is warranted to improve the method, particularly with respect to removing or reducing the artefacts which were shown to impacted reader preference

Cardiovascular magnetic resonance and positron emission tomography in the assessment of aortic stenosis

Background Aortic stenosis is not only characterized by progressive valve narrowing but also by the hypertrophic response of the left ventricle that ensues. In this most common valvular condition novel imaging approaches (cardiovascular magnetic resonance [CMR] and positron emission tomography [PET]) have shown promise in the assessment of disease progression and risk stratification. The central aim of this thesis was to investigate the potential of CMR imaging to refine risk prediction and to improve the imaging protocol of 18F-sodium fluoride PET for aortic stenosis. Methods and Results Asymmetric wall thickening in aortic stenosis In a prospective observational cohort study, 166 patients with aortic stenosis (age 69, 69% males, mean aortic valve area 1.0±0.4cm2) and 37 age and sex-matched healthy volunteers underwent phenotypic characterisation with comprehensive clinical, imaging and biomarker evaluation. Asymmetric wall thickening on both echocardiography and cardiovascular magnetic resonance was defined as regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Asymmetric wall thickening was observed in 26% (n=43) of patients with aortic stenosis using magnetic resonance and 17% (n=29) using echocardiography. Despite similar demographics, co-morbidities, valve narrowing, myocardial hypertrophy and fibrosis, patients with asymmetric wall thickening had increased cardiac troponin I and brain natriuretic peptide concentrations (both p<0.001). Over 28 [22, 33] months of follow-up, asymmetric wall thickening was an independent predictor of aortic valve replacement or death whether detected by magnetic resonance (HR=2.15; 95 CI 1.29 to 3.59; p=0.003) or echocardiography (HR=1.79; 95 CI 1.08 to 3.69; p=0.021). Animal model of pressure overload We performed serial Cardiac Magnetic Resonance (CMR) imaging every 2-week in 31 mice subjected to pressure overload (continuous angiotensin II infusion) for 6 weeks and investigated reverse remodelling by repeating CMR 1 month following normalization of afterload (n=9). Cine CMR was used to measure left ventricular volumes, mass, and systolic function whilst myocardial fibrosis was assessed using indexed ECV (iECV) calculated from T1-relaxation times acquired with a small animal modified look-locker inversion recovery sequence. During the initial phase of increased pressure afterload indices of left ventricular hypertrophy (0.091 [0.083, 0.105] vs 0.123 [0.111, 0.138] g) and myocardial fibrosis (iECV: 0.022 [0.019, 0.024] vs 0.022 [0.019, 0.024] mL) increased in line with blood pressure measurements (65.1±12.0 vs 84.7±9.2 mmHg) whilst left ventricular ejection fraction (LVEF, 59.3 [57.6, 59.9] vs 46.9 [38.5, 49.6] %) deteriorated significantly (all p≤0.01 compared to baseline). During the reverse remodelling phase blood pressure normalized (68.8±5.4 vs 65.1±12.0 mmHg, p=0.42 compared to baseline). Whilst LV mass (0.108 [0.098, 0.116] vs 0.091 [0.083, 0.105] g) and iECV (0.034 [0.032, 0.036] vs 0.022 [0.019, 0.024] mL) improved both remained elevated compared to baseline (p<0.05). Similarly, the LVEF remained impaired 51.1 [42.9, 52.8] vs 59.3 [57.6, 59.9] %, p=0.03. There was a strong association between LVEF and iECV values during pressure overload (r=-0.88, p<0.001). Gender differences in aortic stenosis Two hundred forty-nine patients (66±13 years, 30% women) with at least mild AS were recruited from two prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR exams. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis. There was no difference in age between women and men (66±15 vs 66±12 years, p=0.78). However, women presented a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all p≤0.10). As expected, LV mass index measured by CMR was smaller in women than in men (p<0.0001). Despite fewer comorbidities, women presented larger ECV fraction [29.0 (27.4-30.6) vs. 26.8 (25.1-28.7) %, p<0.0001] and similar LGE [4.5 (2.3- 7.0) vs. 2.8 (0.6-6.8) %, p=0.20] than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (both p≤0.05). Prior CT angiography for PET Forty-five patients (age 67.1±6.9 years, 76% males) underwent CTA (CTA1) and combined 18F-NaF PET/CTA (CTA2) imaging within 14 [10,21] days. We fused CTA1 from visit one with 18F-NaF PET from the second visit (PET) and compared visual pattern of activity, maximal standard uptake values (SUVmax) and target to background (TBR) measurements on (PET/CTA1) fused versus hybrid (PET/CTA2) data. On PET/CTA2, 226 coronary plaques were identified. Fifty-eight coronary segments from 28 (62%) patients had high 18F-NaF uptake (TBR>1.25), whilst 168 segments had lesions with 18F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on co-registered PET/CTA1. There was no significant difference in 18F-NaF uptake values between PET/CTA1 and PET/CTA2 (SUVmax: 1.16±0.40 vs. 1.15±0.39, p=0.53; TBR:1.10±0.45 vs. 1.09±0.46, p=0.55). The intraclass correlation coefficient for SUVmax and TBR was 0.987 (95%CI 0.983 to 0.991) and 0.986 (95%CI 0.981 to 0.992). There was no fixed or proportional bias between PET/CTA1 and PET/CTA2 for SUVmax and TBR. Cardiac motion correction of PET scans improved reproducibility with tighter 95% limits of agreement (±0.14 for SUVmax and ±0.15 for TBR vs. ±0.20 and ±0.20 on diastolic imaging; p<0.001). Delayed PET imaging Twenty patients (67±7years old, 55% male) with stable coronary artery disease underwent coronary CT angiography and PET/CT both 1 h and 3 h after the injection of 266.2±13.3 MBq of 18F-NaF. We compared the visual pattern of coronary uptake, maximal background (blood pool) activity, noise, standard uptake values (SUVmax), corrected SUV (cSUVmax) and target to background (TBR) measurements in lesions defined by CTA on 1h vs 3h post injection 18F-NaF PET. On 1h PET 26 CTA lesions with 18F-NaF PET uptake were identified in 12 (60%) patients. On 3h PET we detected 18F-NaF PET uptake in 7 lesions which were not identified on the 1h PET. The median cSUVmax and TBR values of these lesions were 0.48 [interquartile range (IQR) 0.44-0.51] and 1.45 [IQR, 1.39-1.52] compared to -0.01 [IQR, -0.03-0.001] and 0.95 [IQR, 0.90-0.98] on 1h PET, both p<0.001. Across the entire cohort 3h PET SUVmax values were similar to 1h PET measurements 1.63 [IQR, 1.37-1.98] vs. 1.55 [IQR, 1.43-1.89], p=0.30 and the background activity was lower 0.71 [IQR, 0.65-0.81] vs. 1.24 [IQR, 1.05-1.31], p<0.001. On 3h PET, the TBR values, cSUVmax and the noise were significantly higher (2.30 [IQR, 1.70-2.68] vs 1.28 [IQR, 0.98-1.56], p<0.001; 0.38 [IQR, 0.27-0.70] vs 0.90 [IQR, 0.64-1.17], p<0.001 and 0.10 [IQR, 0.09-0.12] vs. 0.07 [IQR, 0.06-0.09], p=0.02). The median cSUVmax and TBR values increased by 92% (range: 33-225%) and 80% (range: 20-177%). Conclusions In aortic stenosis, asymmetric wall thickening is associated with adverse prognosis, in this condition there are significant differences in the fibrosis burden between male and female patients and the adverse remodeling of the ventricle can be reproduced in a simple animal model of pressure overload. For 18F-NaF PET utilizing a CT angiography acquired before the PET acquisition enables adequate uptake quantification and delayed emission scanning facilitates image analysis

Assessing the impact of motion on treatment planning during stereotactic body radiotherapy of lung cancer

Cancer is a leading cause of death in Australia and approximately 52% of cancer patients will require radiotherapy at some stage in their treatment. In recent years, stereotactic radiotherapy has emerged as an increasingly common treatment modality for small lesions in various sites of the human body.  To facilitate the investigation into the effects of imaging small mobile lesions, a see-saw 4D-CT phantom was developed. This phantom was used to investigate phase-binning artifacts that can be present when assigning an insufficient number of phases to 4D-CT data. The interplay between a lesion’s size and its amplitude, and the effects this relationship has on 4D-CT data was also investigated. An upgrade to a commercially available respiratory motion phantom was also pursued in order to replicate patient motion recorded with the Varian RPM system. Monte Carlo methods were used to determine the impact of motion on PET data by incorporating a computational moving phantom (XCAT) with a full Monte Carlo model of a commercially available PET scanner. To assess the impact of motion on treatment planning and dose calculation, two treatment planning scenarios were simulated using Monte Carlo. The traditional method of calculating dose on an average intensity projection from 4D-CT was compared to 4D dose calculation, in which tumour motion data from 4D-CT is explicitly incorporated into the treatment plan. Monte Carlo methods are also employed to evaluate the degree of underdosage at the periphery of lung lesions arising from electronic disequilibrium associated with density changes.  It was found that small lesions typically seen in SBRT of lung cancer require extra care when considering treatment planning, motion mitigation, and treatment delivery. The upgraded QUASAR phantom allows for patient specific verification of SBRT/SABR treatment plans to be conducted and was found to replicate patient motion accurately. Respiratory analysis software presented in this work enables detailed statistics of a patient’s respiratory characteristics to be evaluated. The number of phase-bins required to mitigate banding artifacts in 4D-CT projections is quantified in a simple equation for sinusoidal motion. It was also found that for lesion with diameters greater than 2.0 cm and amplitudes less than 4.0 cm, ten phase-bins are adequate to negate all banding artifacts in projection images.  Experimental and Monte Carlo simulations of PET and 4D-PET revealed that motion greater than 1.0 cm resulted in a reduction in apparent activity that increased with motion amplitude. A Dose Reduction Factor (DRF) metric was developed using Monte Carlo simulation which is defined as the ratio of the average dose to the periphery of the lesion to the dose in the central portion. The mean DRF was found to be 0.97 and 0.92 for 6 MV and 15 MV photon beams respectively, for lesion sizes ranging from 10 – 50 mm. The dynamic scenario was simulated with 4D dose calculation methods of registering and adding the dose distributions in each phase-bin from 4D-CT. The dose-volume distributions compared well with 3D (AIP) methods if multiple beams were used and the amplitude of motion was less than 3.0 cm.