A dynamic reconstruction approach for cerebral blood flow quantification with an interventional C-arm CT

Tomographic perfusion imaging is a well accepted method for stroke diagnosis that is available with current CT and MRI scanners. A challenging new method, which is currently not available, is perfusion imaging with an interventional C-arm CT that can acquire 4-D images using a C-arm angiography system. This method may help to optimize the workflow du-ring catheter-guided stroke treatment. The main challenge in perfusion C-arm CT is the comparably slow rotational speed of the C-arm (approximately 5 seconds) which decreases the overall temporal resolution. In this work we present a dyna-mic reconstruction approach optimized for perfusion C-arm CT based on temporal estimation of partially backprojected volumes. We use numerical simulations to validate the algo-rithm: For a typical configuration the relative error in estima-ted arterial peak enhancement decreases from 14.6 % to 10.5% using the dynamic reconstruction. Furthermore we present in-itial results obtained with a clinical C-arm CT in a pig model. 1

Dual-energy imaging in stroke : feasibility of dual-layer detector cone-beam computed tomography

Background: Dual-energy computed tomography (DECT) is increasingly available and used in the standard diagnostic setting of ischemic stroke patients. For stroke patients with suspected large vessel occlusion, cone-beam computed tomography (CBCT) in the interventional suite could be an alternative to CT to shorten door to thrombectomy time. This approach could potentially lead to an improved patient outcome. However, image quality in CBCT is typically limited by artifacts and poor differentiation between gray and white matter. A dual-layer detector CBCT (DL-CBCT) system could be used to separate photon energy spectra with the potential to increase visibility of clinically relevant features, and acquire additional information. Purpose: Paper I evaluated how a range of DECT virtual monoenergetic images (VMI) impact identification of early ischemic changes, compared to conventional polyenergetic CT images. Paper II characterized the performance of a novel DLCBCT system with regards to clinically relevant imaging features. Paper III & IV investigated if DL-CBCT VMIs are sufficient for stroke diagnosis in the interventional suite, compared to reference standard CT. Methods: Paper I was a retrospective single-center study including consecutive patients presenting with acute ischemic stroke caused by an occlusion of the intracranial internal carotid artery or proximal middle cerebral artery. Automated Alberta Stroke Program Early Computed Tomography Score (ASPECTS) results from conventional images and 40-120 keV VMI were generated and compared to reference standard CT ASPECTS. In paper II, a prototype dual-layer detector was fitted into a commercial interventional C-arm CBCT system to enable dual-energy acquisitions. Metrics for spatial resolution, noise and uniformity were gathered. Clinically relevant tissue and iodine substitutes were characterized in terms of effective atomic numbers and electron densities. Iodine quantification was performed and virtual non-contrast (VNC) images were evaluated. VMIs were reconstructed and used for CT number estimation and evaluation of contrast-to-noise ratios (CNR) in relevant tissue pairings. In paper III and IV, a prospective single-center study enrolled consecutive participants with ischemic or hemorrhagic stroke on CT. In paper III, hemorrhage detection accuracy, ASPECTS accuracy, subjective and objective image quality were evaluated on non-contrast DL-CBCT 75 keV VMI and compared to reference standard CT. In paper IV, intracranial arterial segment vessel visibility and artifacts were evaluated on intravenous DL-CBCT angiography (DL-CBCTA) 70 keV VMI and compared to CT angiography (CTA). In both paper III and IV, non-inferiority was determined by the exact binomial test with a one-sided lower performance boundary set to 80% (98.75% CI). Main results: In paper I, 24 patients were included. 70 keV VMI had the highest region-based ASPECTS accuracy (0.90), sensitivity (0.82) and negative predictive value (0.94), whereas 40 keV VMI had the lowest accuracy (0.77), sensitivity (0.34) and negative predictive value (0.80). In paper II, the prototype and commercial CBCT had a similar spatial resolution and noise using the same standard reconstruction. For all tissue substitutes, the mean accuracy in effective atomic number was 98.2% (SD 1.2%) and 100.3% (SD 0.9%) for electron density. Iodine quantification had a mean difference of -0.1 (SD 0.5) mg/ml compared to the true concentrations. For VNC images, iodine substitutes with blood averaged 43.2 HU, blood only 44.8 HU, iodine substitutes with water 2.6 HU. A noise-suppressed dataset showed a CNR peak at 40 keV VMI and low at 120 keV VMI. In the same dataset without noise suppression, peak CNR was seen at 70 keV VMI and a low at 120 keV VMI. CT numbers of various clinically relevant objects generally matched the calculated CT number in a wide range of VMIs. In paper III, 27 participants were included. One reader missed a small bleeding, however all hemorrhages were detected in the majority analysis (100% accuracy, CI lower boundary 86%, p=0.002). ASPECTS majority analysis had 90% accuracy (CI lower boundary 85%, p<0.001), sensitivity was 66% (individual readers 67%, 69% and 76%), specificity was 97% (97%, 96% and 89%). Subjective and objective image quality metrics were inferior to CT. In paper IV, 21 participants had matched image sets. After excluding examinations with scan issues, all readers considered DL-CBCTA non-inferior to CTA (CI boundary 93%, 84%, 80%, respectively), when assessing arteries relevant in candidates for intracranial thrombectomy. Artifacts were more prevalent compared to CTA. Conclusions: In paper I, automated 70 keV VMI ASPECTS had the highest diagnostic accuracy, sensitivity and negative predictive value overall. Different VMI energy levels impact the identification of early ischemic changes on DECT. In paper II, the DL-CBCT prototype system showed comparable technical metrics to a commercial CBCT system, while offering dual-energy capability. The dual-energy images indicated a consistent ability to separate and characterize clinically relevant tissues, blood and iodine. Thus, the DL-CBCT system could find utility in the diagnostic setting. In paper III, non-contrast DL-CBCT 75 keV VMI showed non-inferior hemorrhage detection and ASPECTS accuracy to CT. However, image quality was inferior compared to CT, and visualization of small subarachnoid hemorrhages after treatment remains a challenge. In the same stroke cohort, paper IV showed non-inferior vessel visibility for DL-CBCTA 70 keV VMI compared to CTA under certain conditions. Specifically, the prototype system had a long scan time and was not capable of bolus tracking which resulted in scan issues. After excluding participants with such issues, DL-CBCTA 70 keV VMI were found non-inferior to CTA. In summary, the findings of this thesis indicate that DL-CBCT may be sufficient for stroke assessment in the interventional suite with the potential to bypass CT in patients eligible for thrombectomy. However, issues related to the prototype system and the visualization of small hemorrhages highlight the need of further development

Guest Editorial Special Issue on Medical Imaging and Image Computing in Computational Physiology

International audienceThe January 2013 Special Issue of IEEE transactions on medical imaging discusses papers on medical imaging and image computing in computational physiology. Aslanid and co-researchers present an experimental technique based on stained micro computed tomography (CT) images to construct very detailed atrial models of the canine heart. The paper by Sebastian proposes a model of the cardiac conduction system (CCS) based on structural information derived from stained calf tissue. Ho, Mithraratne and Hunter present a numerical simulation of detailed cerebral venous flow. The third category of papers deals with computational methods for simulating medical imagery and incorporate knowledge of imaging physics and physiology/biophysics. The work by Morales showed how the combination of device modeling and virtual deployment, in addition to patient-specific image-based anatomical modeling, can help to carry out patient-specific treatment plans and assess alternative therapeutic strategies

3D Imaging for Planning of Minimally Invasive Surgical Procedures

Novel minimally invasive surgeries are used for treating cardiovascular diseases and are performed under 2D fluoroscopic guidance with a C-arm system. 3D multidetector row computed tomography (MDCT) images are routinely used for preprocedural planning and postprocedural follow-up. For preprocedural planning, the ability to integrate the MDCT with fluoroscopic images for intraprocedural guidance is of clinical interest. Registration may be facilitated by rotating the C-arm to acquire 3D C-arm CT images. This dissertation describes the development of optimal scan and contrast parameters for C-arm CT in 6 swine. A 5-s ungated C-arm CT acquisition during rapid ventricular pacing with aortic root injection using minimal contrast (36 mL), producing high attenuation (1226), few artifacts (2.0), and measurements similar to those from MDCT (p\u3e0.05) was determined optimal. 3D MDCT and C-arm CT images were registered to overlay the aortic structures from MDCT onto fluoroscopic images for guidance in placing the prosthesis. This work also describes the development of a methodology to develop power equation (R2\u3e0.998) for estimating dose with C-arm CT based on applied tube voltage. Application in 10 patients yielded 5.48┬▒177 2.02 mGy indicating minimal radiation burden. For postprocedural follow-up, combinations of non-contrast, arterial, venous single energy CT (SECT) scans are used to monitor patients at multiple time intervals resulting in high cumulative radiation dose. Employing a single dual-energy CT (DECT) scan to replace two SECT scans can reduce dose. This work focuses on evaluating the feasibility of DECT imaging in the arterial phase. The replacement of non-contrast and arterial SECT acquisitions with one arterial DECT acquisition in 30 patients allowed generation of virtual non-contrast (VNC) images with 31 dose savings. Aortic luminal attenuation in VNC (32┬▒177 2 HU) was similar to true non-contrast images (35┬▒177 4 HU) indicating presence of unattenuated blood. To improve discrimination between c

Shear-promoted drug encapsulation into red blood cells: a CFD model and μ-PIV analysis

The present work focuses on the main parameters that influence shear-promoted encapsulation of drugs into erythrocytes. A CFD model was built to investigate the fluid dynamics of a suspension of particles flowing in a commercial micro channel. Micro Particle Image Velocimetry (μ-PIV) allowed to take into account for the real properties of the red blood cell (RBC), thus having a deeper understanding of the process. Coupling these results with an analytical diffusion model, suitable working conditions were defined for different values of haematocrit

3D Imaging for Planning of Minimally Invasive Surgical Procedures

Novel minimally invasive surgeries are used for treating cardiovascular diseases and are performed under 2D fluoroscopic guidance with a C-arm system. 3D multidetector row computed tomography (MDCT) images are routinely used for preprocedural planning and postprocedural follow-up. For preprocedural planning, the ability to integrate the MDCT with fluoroscopic images for intraprocedural guidance is of clinical interest. Registration may be facilitated by rotating the C-arm to acquire 3D C-arm CT images. This dissertation describes the development of optimal scan and contrast parameters for C-arm CT in 6 swine. A 5-s ungated C-arm CT acquisition during rapid ventricular pacing with aortic root injection using minimal contrast (36 mL), producing high attenuation (1226), few artifacts (2.0), and measurements similar to those from MDCT (p\u3e0.05) was determined optimal. 3D MDCT and C-arm CT images were registered to overlay the aortic structures from MDCT onto fluoroscopic images for guidance in placing the prosthesis. This work also describes the development of a methodology to develop power equation (R2\u3e0.998) for estimating dose with C-arm CT based on applied tube voltage. Application in 10 patients yielded 5.48┬▒177 2.02 mGy indicating minimal radiation burden. For postprocedural follow-up, combinations of non-contrast, arterial, venous single energy CT (SECT) scans are used to monitor patients at multiple time intervals resulting in high cumulative radiation dose. Employing a single dual-energy CT (DECT) scan to replace two SECT scans can reduce dose. This work focuses on evaluating the feasibility of DECT imaging in the arterial phase. The replacement of non-contrast and arterial SECT acquisitions with one arterial DECT acquisition in 30 patients allowed generation of virtual non-contrast (VNC) images with 31 dose savings. Aortic luminal attenuation in VNC (32┬▒177 2 HU) was similar to true non-contrast images (35┬▒177 4 HU) indicating presence of unattenuated blood. To improve discrimination between c

Carotid Ultrasound for Stroke Prediction

Introduction: The aims of this thesis were to identify if carotid endarterectomy was cost-effective and affordable in the United Kingdom and secondly to explore the potential of contrast enhanced ultrasound and plaque texture analysis for risk stratification in asymptomatic patients with carotid atherosclerosis. Methods: A cost-utility analysis based on results from the Asymptomatic Carotid Surgery Trial was performed using a Markov transition state model. Three cross-sectional studies of symptomatic and asymptomatic individuals with 50-99% carotid stenosis were performed for late phase and dynamic phase contrast enhanced ultrasound, followed by plaque texture analysis. Results: There was a high probability of surgical endarterectomy lying under the £20-30, 000 per quality adjusted life year National Institute for Health and Clinical Excellence acceptability threshold in the United Kingdom. In men under 75 years of age, the cost per quality adjusted life year gained was lower and in women there was improved effectiveness with reduced long-term costs. Late phase contrast enhanced ultrasound imaging of carotid atherosclerosis suffered from a tissue suppression artefact which limited its ability to image microbubble retention. Quantification of plaque perfusion using low mechanical index imaging demonstrated a pseudoenhancement phenomenon from non-linear propagation, which artificially increased far wall intensity, again limiting its use for quantification of plaque perfusion. Semi-quantitative grading of plaque perfusion revealed no significant difference in generalised plaque perfusion between symptomatic and asymptomatic individuals, however detection of ulceration using dynamic contrast enhanced ultrasound showed a trend towards an association with symptomatic status. Type II plaque showed a significant independent association with symptomatic status. Conclusion: Carotid endarterectomy is likely to be cost-effective in those under 75 years of age, particularly women. However, without further selection, the upfront costs and high number needed to treat with endarterectomy limit its potential as a large scale strategy. Improvements in non-linear pulse sequencing are required before quantitative contrast enhanced ultrasound can reliably be used for functional imaging of carotid atherosclerosis. Qualitative assessment of plaque perfusion is unlikely to gain widespread use due to its high subjectivity. However assessment of plaque type and to a lesser extent imaging of ulceration using contrast enhanced ultrasound are promising and reproducible imaging biomarkers for further study. Validation of these markers with histology and then prospective study of individuals with these plaque phenotypes is proposed. In the future individuals with a recent transient ischaemic attack and moderate (50-69%) stenosis may prove to be an ideal group for risk stratification

Applications of CT Perfusion-Based Triaging and Prognostication in Acute Ischemic Stroke

CT Perfusion (CTP) is a minimally invasive imaging technique that aids acute ischemic stroke (AIS) triage and prognostication by determining tissue viability based on hemodynamic parameters. The goals of this research are to determine: 1) CTP thresholds for estimation of infarct and penumbra volume, 2) how CTP scan duration impacts infarct and penumbra volume estimates, and 3) reliability of CTP for predicting functional outcomes following intra-arterial therapy (IAT). Chapter 2 introduced an experimental study for determining ischemia-time dependent thresholds for brain infarction using multimodal imaging in a porcine stroke model that is easier to implement than previous large animal stroke models. CTP determined an absolute cerebral blood flow (CBF) threshold of 12.6±2.8mL∙min-1∙100g-1 for brain infarction after 3h of ischemia, which was close to that derived using hydrogen clearance in a previous study by Jones et al (Journal of Neurosurgery, 1981;54(6):773-782). Chapter 3 retrospectively investigated the impact of CTP scan duration on cerebral blood volume (CBV), CBF, and time-to-maximum (Tmax) and found optimal scan durations that minimized radiation dose while not under- or over-estimating infarct volumes measured using two previously derived CBF thresholds for infarction. We found that CBV and Tmax decreased at shorter scan durations, whereas CBF was independent of scan duration, consequently, infarct volume estimated by both CBF thresholds was independent of scan duration. Chapter 4 compared reperfusion seen on follow-up CTP to reperfusion predicted by post-IAT digital subtraction angiography (DSA) and the ability of the two modalities to predict good 90-day functional outcome in a retrospective study. We found that patients with ‘complete reperfusion’ grades on DSA often had ischemic tissue on follow-up CTP and that follow-up CTP had superior specificity and accuracy for predicting functional outcome compared to DSA. In summary, this research has shown that CBF thresholds can reliably detect infarct in AIS and are independent of scan duration, allowing radiation dose to be minimized by limiting scans to 40s without compromising accuracy of infarct volume estimates. Finally, CTP is a more specific and accurate predictor of functional outcome than the commonly used post-procedural DSA, this could help select patients for neuroprotective therapy

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world